Gynaecological Follow-up of a Subset of HPV-015 Study Subjects
Phase: PHASE3
Conditions: Infections, Papillomavirus
Sponsor: GlaxoSmithKline

Protocol and Protocol Amendments
 
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Clinical Study Protocol
Sponsor:
GlaxoSmithKline Biologicals
Rue de l’Institut 89
B-1330 Rixensart, Belgium
Primary Study vaccine and 
number 
No vaccines are administered in this study.
GlaxoSmithKline Biologicals’ candidate human
papillomavirus (HPV) vaccine containing HPV-
16/18 L1 VLP proteins and AS04 adjuvant (GSK 
580299) was administered in the primary HPV-015 
study.
Other Study vaccines
No vaccines are administered in this study.
eTrack study number and 
Abbreviated Title(s)
113617 (HPV-062 EXT:015)
Investigational New Drug 
(IND) number
BB-IND 7920
EudraCT number
2009-017282-35
Date of protocol
Final: 03 March 2010
Date of protocol amendment 1
Amendment 1: 21 June 2010
Date of protocol 
administrative change 1
Administrative Change 1 Final: 18 August 2010
Title
Gynaecological follow-up of a subset of HPV-015 
study subjects
Detailed Title
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of 
HPV-015 study subjects
Co-ordinating author
 Scientific Writer
Contributing authors
 Clinical Development Manager
 Director, Clinical Development 
 Project Statistician
 Global Study Manager
 Global Study Manager
 Global Study Manager
 Regulatory Affairs 
Representative
 External Laboratory Coordinator
 Clinical Safety 
Representative
 Clinical Safety Representative
 Clinical Data Coordinator
GSK Biologicals’ Protocol DS v 13.0
Copyright 2010 the GlaxoSmithKline group of companies. All rights reserved. Unauthorised 
copying or use of this information is prohibited.
 
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PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Protocol Administrative Change 1 Sponsor Signatory Approval
eTrack study number and 
Abbreviated Title
113617 (HPV-062 EXT:015)
IND number
BB-IND 7920
EudraCT number
2009-017282-35
Date of protocol
Final: 03 March 2010
Date of protocol
amendment 1
Amendment 1 Final: 21 June 2010
Date of protocol 
administrative change 1
Administrative Change 1 Final: 18 August 2010
Detailed Title 
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of HPV-
015 study subjects
Sponsor signatory
Dominique Descamps, MD,
Director, Clinical Development
GlaxoSmithKline Biologicals
Rue de l’Institut 89
B-1330 Rixensart
Belgium
Signature
Date
 
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Protocol Administrative Change 1 Rationale
Administrative Change 
number:
Administrative Change 1
Rationale/background for changes:
Since the double-blind study HPV-015 will be extended by a maximum of three 
additional years, according to Protocol Amendment 4, dated 24 March 2010, it is 
important that central study staff involved in the studies remains blinded till the end of 
study HPV-015 for all subjects who have been participating in HPV-015 and will be 
participating in this study. Therefore, subjects enrolled in HPV-015 extension studies 
such as study HPV-062 cannot retain the HPV-015 subject number as is stated in the 
original protocol. Consequently, different identification numbers will be provided by 
an external statistician.
 
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Protocol Administrative Change 1 Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any mutually agreed future 
protocol amendments or protocol administrative changes, and with any other study 
conduct procedures and/or study conduct documents provided by GlaxoSmithKline 
Biologicals (GSK Biologicals).

To assume responsibility for the proper conduct of the study at this site.

That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.

To ensure that all persons assisting me with the study are adequately informed about 
the GSK Biologicals investigational product(s) and other study-related duties and 
functions as described in the protocol.

To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual.

To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK Biologicals and the express written informed 
consent of the subject and/or the subject’s legally authorised representative. 

To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s). 

To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data.

That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational product, and more generally about his/her financial 
ties with the sponsor. GSK Biologicals will use and disclose the information solely 
for the purpose of complying with regulatory requirements.
Hence I:

Agree to supply GSK Biologicals with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children).

Agree to promptly update this information if any relevant changes occur during the 
course of the study and for 1 year following completion of the study. 

Agree that GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities.

Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study.
 
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eTrack study number(s) 
and Abbreviated Title(s)
113617 (HPV-062 EXT:015)
IND number
BB-IND 7920
EudraCT number
2009-017282-35
Date of protocol
Final: 03 March 2010
Date of protocol 
amendment 1
Amendment 1 Final: 21 June 2010
Date of protocol 
administrative change 1
Administrative Change 1 Final: 18 August 2010
Detailed Title
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of HPV-
015 study subjects
Investigator name
Signature
Date
Leiter der klinischen 
Prüfung’ (LKP) name
Signature
Date
 
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SYNOPSIS
Detailed Title
A phase IIIb, open, multi-centre gynaecological extension 
study for the follow-up of a subset of HPV-015 study subjects.
Indication
Cervarix is indicated in females from 10 years of age onwards 
for the prevention of persistent infection, premalignant 
cervical lesions and cervical cancer (squamous-cell carcinoma 
and adenocarcinoma) caused by oncogenic Human 
Papillomaviruses (HPV).
This HPV-16/18 L1 VLP AS04 vaccine was administered to 
the HPV-015 study vaccine group. Cross-over vaccination 
will be offered to the subjects in the HPV-015 control group 
either by providing commercially available HPV-16/18 L1 
VLP AS04 vaccine or, if the vaccine is not licensed in the 
considered country or not licensed for the respective age 
group, through a separate clinical trial protocol. No vaccine 
will be administered in the current study. 
Rationale for the 
study and study 
design
This study will be conducted to allow for a safe exit from the 
HPV-015 study, ensuring that women who are at risk of 
developing a gynaecological lesion are medically monitored.
Study subjects enrolled in the control arm of HPV-015 study 
may have been infected with the HPV types included in the 
vaccine during the study. All subjects may have been exposed 
to other high-risk HPV types. 
The current study will provide annual oncogenic HPV DNA 
testing and cervical cytology examination for a subset of 
HPV-015 subjects, who at their concluding HPV-015 study 
visit: 

displayed normal cervical cytology but tested 
positive for oncogenic HPV infection

were pregnant so that no cervical sample could be 
collected
For eligible subjects, the duration of this gynaecological 
follow-up will be up to a maximum of four years after the 
subjects’ concluding visit of study HPV-015, since most 
cervical lesions develop within four years of infection and 
most oncogenic HPV infections are estimated to clear within 
two years [Trottier, 2008].
If very few subjects are eligible for this study at one HPV-015 
study site and if adequate gynaelogical follow-up care is 
available through the local health care system, these subjects 
may be referred to the local health care system, provided that 
ethical committee approval is obtained by the responsible 
investigator.
The initial protocol of the HPV-015 trial included a three-year 
 
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efficacy follow-up. The HPV-015 protocol amendment 3 and 
4 extended the HPV-015 trial by one and up to a maximum of 
three additional years, respectively. Subjects may however 
decide to conclude their participation in the HPV-015 study at 
Visit 9, Visit 11 or at the last study visit in HPV-015 planned 
under protocol amendment 4.
Note that subjects enrolled in this study can also concurrently 
participate in a GSK Biologicals study to receive cross-over 
vaccination.
This study is not intended to collect long-term efficacy, 
immunogenicity or safety follow-up data. Long-term data for 
GSK Biologicals’ HPV vaccine will be obtained through other 
studies.
Study objectives

To provide clinical management and, if required,
treatment to subjects who at their concluding HPV-015 
study visit displayed normal cervical cytology but tested 
positive for oncogenic HPV infection or who were 
pregnant at their concluding visit of the HPV-015 study 
so that no cervical sample could be collected.
Study design

Experimental design: A phase IIIb, open, multi-centre 
study with one group.

Treatment allocation: None.

Blinding: Open.

HPV-015 concluding visit: Subjects who participated in 
the HPV-015 study may decide to conclude their
participation in the HPV-015 study at Visit 9, Visit 11 or 
at the last study visit in HPV-015 planned under protocol 
amendment 4.

Treatment groups: One study group consisting of a
subset of HPV-015 subjects who at their concluding
HPV-015 study visit:

displayed normal cervical cytology but tested 
positive for oncogenic HPV infection 

were pregnant so that no cervical sample could be 
collected at that visit 

Vaccination schedule(s): None.

Control: None.

Type of study: Gynaecological follow-up extension 
study of a subset of HPV-015 study subjects.

Data collection: Remote Data Entry (RDE).

Duration of the study: Maximum of four years for each 
 
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subject.

Study visits per subject: Up to four scheduled visits at 
approximately Months 12, 24, 36 and 48 after each 
subject’s concluding HPV-015 study visit
Subjects are eligible to join the study at any visit.

Study procedures:
Subjects will enter the study approximately one year after 
their HPV-015 concluding study visit. Annual visits will 
be scheduled for a maximum study duration of 
approximately four years
At each visit, a gynaecological examination will be 
performed and cervical liquid-based cytology samples 
will be collected for cervical cytology examination and 
oncogenic HPV DNA testing, if the cytology reading is 
normal or ASCUS.
The presence of oncogenic HPV infection will be 
determined by the Hybrid Capture® II (HCII) test, which 
detects HPV DNA types 16, 18, 31, 33, 35, 39, 45, 51, 
52, 56, 58, 59 and 68 [Vernick 2003, Digene Corporation 
2002]. Cervical cytology examination will be performed 
using the ThinPrep®Pap test.
Continued study participation as well as further 
referral/treatment will be based on the test results from 
each visit, and will be aligned with the clinical 
management algorithm which is aligned with the 2009 
American Society for Colposcopy and Cervical Pathology 
(ASCCP) guidelines for use of HPV DNA testing as an 
adjunct to cytology for cervical cancer screening in 
women 30 years or older.
The following clinical management algorithm will be 
applied:

Subjects with normal cervical cytology and who are 
oncogenic HPV DNA negative, will end their 
participation in the study.

Subjects with normal cervical cytology, but who are 
oncogenic HPV DNA positive in one single test, will 
be asked to return at the next study visit.
This outcome will only be applicable to subjects who 
were pregnant at their concluding HPV-015 study 
visit so that no cervical sample could be collected at 
that visit.

Subjects with normal cervical cytology, but who are 
oncogenic HPV DNA positive in two subsequent 
tests, will be referred to colposcopy. The result of the 
 
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subjects’ concluding HPV-015 study visit will be 
taken into account at Visit 1.

Subjects with a single cervical cytology reading of 
ASC-US (atypical squamous cells of undetermined 
significance) positive for oncogenic HPV DNA will 
be referred to colposcopy.

Subjects with a single cervical cytology reading of 
LSIL (low grade squamous intraepithelial lesion) 
will be referred to colposcopy.
Please note that a missing result for HCII will be 
managed as oncogenic HPV positive.
In case of referral for colposcopy, the post-colposcopy 
follow-up strategies are:

If no lesion is detected or the detected lesion does not 
require any treatment, subjects will be asked to return 
at the next study visit. 

If a lesion that requires treatment is detected, the 
subject should be referred to treatment according to 
local medical practice. Any further management 
following local cervical therapy for cervical lesions 
will be handled according to local medical practice 
within the local health care system. After treatment, 
the subject’s participation in the study will end.
As management algorithms cannot define every clinical 
situation, it is the investigator’s (or his/her designee’s) 
responsibility to exercise appropriate clinical judgement 
in the medical management of each individual case.
Once their study participation ends, all subjects should be 
referred to their local health care system. 
Subjects who have not developed cervical lesions by the 
end of the study, but who are still positive for oncogenic 
HPV infection, should be informed of the potential risks 
of being positive for oncogenic HPV DNA and the 
importance of continued follow-up.

Study visit activities and gynaecological follow-up 
reporting

Gynaecological examination at Visit 1, Visit 2, Visit 
3 and Visit 4.

Collection of cervical liquid-based cytology samples 
at Visit 1, Visit 2, Visit 3 and Visit 4 for cervical 
cytology examination and oncogenic HPV DNA 
testing, if the cytology reading is normal or ASCUS.
 
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
Referral to colposcopy according to protocol clinical 
management algorithm, if required.

Conduct of colposcopy, colposcopy directed biopsies 
and local cervical therapy according to local medical 
practice, if required.

Recording of colposcopic referral according to 
management algorithm, if required.

Recording of treatment referrals according to local 
medical practice, if required.

Safety reporting:

All fatal SAEs will be reported.

All SAEs assessed as being possibly related to study 
participation will be reported.

All SAEs assessed as being possibly related to a 
concurrent GSK medication will be reported.

Withdrawal from the study due to adverse events 
(AEs) or SAEs will be reported.
No other AEs or SAEs for HPV-015 study subjects will be 
reported in this study. AEs and SAEs related to the vaccine 
administrated in the HPV-015 trial should be reported as part 
of the HPV-015 study, as described in the HPV-015 study 
protocols.
Number of subjects
Approximately 1500 HPV-015 study subjects are expected to 
be eligible to participate in this study.
Study endpoints 

Occurrence of positive oncogenic HPV DNA results in 
cervical samples by HPV DNA testing (Hybrid Capture® 
II test [HCII]).

Occurrence of cervical cytological abnormalities in 
cervical samples by ThinPrep® PapTest.

Occurrence of referral to colposcopy.

Occurrence of referral to treatment.
Study analysis
All study endpoints are descriptive, no inferential analyses 
will be performed.
 
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TABLE OF CONTENTS
PAGE
SYNOPSIS......................................................................................................................6
LIST OF ABBREVIATIONS...........................................................................................16
GLOSSARY OF TERMS ...............................................................................................18
1.
INTRODUCTION....................................................................................................20
1.1.
Background ................................................................................................20
1.2.
Rationale for the study and study design ....................................................22
1.2.1.
Rationale for the use of placebo ..................................................22
2.
STUDY OBJECTIVES............................................................................................23
3.
STUDY DESIGN OVERVIEW ................................................................................23
4.
STUDY COHORT...................................................................................................27
4.1.
Number of subjects.....................................................................................27
4.2.
Inclusion criteria..........................................................................................27
4.3.
Exclusion criteria for enrolment...................................................................28
5.
CONDUCT OF THE STUDY ..................................................................................28
5.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................28
5.2.
Subject identification and randomisation of treatment .................................29
5.2.1.
Subject identification (Administrative change 1)...........................29
5.2.2.
Randomisation of treatment.........................................................29
5.2.3.
Randomisation of subjects to assay subsets................................29
5.3.
Method of blinding ......................................................................................29
5.4.
General study aspects ................................................................................29
5.4.1.
Cytology Report Terminology.......................................................30
5.4.2.
Histopathology Report Terminology.............................................31
5.4.3.
Clinical Management Algorithm ...................................................31
5.4.4.
Unsatisfactory cytological findings ...............................................31
5.4.5.
Abnormal cytology .......................................................................31
5.5.
Colposcopic evaluation...............................................................................31
5.6.
Management of cervical lesions..................................................................32
5.7.
Outline of study procedures ........................................................................32
5.8.
Detailed description of study procedures ....................................................33
5.8.1.
Procedures prior to study participation.........................................34
5.8.1.1.
Informed consent........................................................34
5.8.2.
Procedures during study participation..........................................34
5.8.2.1.
Check inclusion and exclusion criteria ........................34
5.8.2.2.
Collect demographic data...........................................34
5.8.2.3.
Gynaecological examination.......................................34
5.8.2.4.
Cervical sampling .......................................................34
5.8.2.5.
Review oncogenic HPV infection status and 
cervical cytology status...............................................35
 
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5.8.2.6.
Recording of referral to colposcopy and 
treatment (if applicable)..............................................35
5.8.2.7.
Recording of concomitant medication.........................35
5.8.2.8.
Review of continued study participation......................35
5.8.2.9.
Reporting of non-serious AEs and SAEs ....................35
5.8.2.10.
Study conclusion ........................................................35
5.9.
Biological Sample handling and analysis ....................................................35
5.9.1.
Use of specified study materials ..................................................36
5.9.2.
Biological samples.......................................................................36
5.9.3.
Laboratory assays .......................................................................36
5.9.4.
Biological samples evaluation......................................................37
5.9.4.1.
Cytology .....................................................................37
5.9.4.2.
HPV DNA Testing by Hybrid Capture II (HCII)............38
5.9.5.
Immunological correlates of protection.........................................38
6.
STUDY VACCINE AND ADMINISTRATION...........................................................38
6.1.
Concomitant medication/vaccination...........................................................38
6.1.1.
Time window for recording concomitant 
medication/vaccination in the eCRF.............................................39
7.
HEALTH ECONOMICS ..........................................................................................39
8.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS.....................................39
8.1.
Safety definitions ........................................................................................39
8.1.1.
Definition of an adverse event......................................................39
8.1.2.
Examples of an AE DO NOT include: ..........................................40
8.1.3.
Definition of a serious adverse event ...........................................40
8.1.4.
Solicited adverse events..............................................................41
8.1.5.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................41
8.2.
Events or outcomes not qualifying as adverse events or serious 
adverse events ...........................................................................................42
8.2.1.
Pregnancy ...................................................................................42
8.3.
Detecting and recording adverse events, serious adverse events 
and pregnancies .........................................................................................42
8.3.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.....................................42
8.3.2.
Evaluation of adverse events and serious adverse events...........43
8.3.2.1.
Active questioning to detect adverse events 
and serious adverse events........................................43
8.3.2.2.
Assessment of adverse events...................................44
8.3.2.2.1.
Assessment of intensity..........................44
8.3.2.2.2.
Assessment of causality .........................44
8.3.2.3.
Assessment of outcomes............................................45
8.4.
Reporting and follow-up of adverse events, serious adverse events...........45
8.4.1.
Prompt reporting of serious adverse events to GSK 
Biologicals ...................................................................................45
8.4.2.
Regulatory reporting requirements for serious adverse 
events..........................................................................................46
8.4.3.
Completion and transmission of SAEs reports to GSK 
Biologicals ...................................................................................46
 
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8.4.3.1.
Back-up system in case the electronic SAE 
reporting system does not work..................................46
8.4.4.
Follow-up of adverse events and serious adverse events............47
8.5.
Treatment of adverse events ......................................................................48
8.6.
Unblinding...................................................................................................48
8.7.
Emergency unblinding ................................................................................48
8.8.
Subject card................................................................................................49
9.
SUBJECT COMPLETION AND WITHDRAWAL.....................................................49
9.1.
Subject completion .....................................................................................49
9.2.
Subject withdrawal......................................................................................50
9.2.1.
Subject withdrawal from the study ...............................................50
9.2.2.
Subject withdrawal from investigational vaccine/product..............50
9.3.
Extension study ..........................................................................................50
10. DATA EVALUATION: CRITERIA FOR EVALUATION OF OBJECTIVES...............51
10.1.
Study endpoints..........................................................................................51
10.2.
Estimated sample size................................................................................51
10.3.
Study cohorts to be evaluated.....................................................................51
10.4.
Derived and transformed data.....................................................................51
10.5.
Conduct of analyses ...................................................................................51
10.5.1.
Sequence of analyses..................................................................51
10.5.2.
Statistical considerations for interim analyses..............................51
10.6.
Statistical methods......................................................................................52
10.6.1.
Analysis of demographics/baseline characteristics ......................52
10.6.2.
Analysis of efficacy ......................................................................52
10.6.3.
Analysis of immunogenicity..........................................................52
10.6.4.
Descriptive analysis of safety.......................................................52
11. ADMINISTRATIVE MATTERS ...............................................................................52
11.1.
Remote Data Entry instructions ..................................................................52
11.2.
Monitoring by GSK Biologicals....................................................................53
11.3.
Archiving of data at study sites ...................................................................54
11.4.
Audits .........................................................................................................54
11.5.
Ownership, confidentiality and publication ..................................................55
11.5.1.
Ownership ...................................................................................55
11.5.2.
Confidentiality ..............................................................................55
11.5.3.
Publication...................................................................................55
12. COUNTRY SPECIFIC REQUIREMENTS...............................................................56
13. REFERENCES.......................................................................................................57
 
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LIST OF TABLES
PAGE
Table 1
List of study procedures .........................................................................33
Table 2
Intervals between study visits.................................................................33
Table 3
Biological samples .................................................................................36
Table 4
Laboratory assays..................................................................................37
Table 5
Reporting periods for adverse events and serious adverse 
events ....................................................................................................43
Table 6
Time frames for submitting SAEs and other events reports to 
GSK Biologicals .....................................................................................45
LIST OF FIGURES
PAGE
Figure 1
Study visits and study procedures..........................................................23
Figure 2 
HPV-062 EXT:015 study eligibility algorithm ..........................................24
Figure 3
Clinical management algorithm ..............................................................26
 
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LIST OF APPENDICES
PAGE
Appendix A
Laboratory assays..................................................................................60
Appendix B
Amendments and Administrative Changes to the Protocol.....................61
 
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LIST OF ABBREVIATIONS
AE
Adverse event
AGC
Atypical glandular cells
AIS
Adenocarcinoma in-situ
ASC-US
Atypical squamous cells of undetermined significance
ASC-H
Atypical squamous cells cannot exclude HSIL
CIN
Cervical intraepithelial neoplasia
CIN1+
Cervical intraepithelial neoplasia as CIN1, CIN2,CIN3, 
adenocarcinoma in-situ and invasive cervical cancer
CIN2+
Cervical intraepithelial neoplasia as CIN2, CIN3,
adenocarcinoma in-situ and invasive cervical cancer.
CRF/eCRF
Case Report Form/electronic Case Report Form
CRA
Clinical Research Associate
FDA
Food and Drug Administration, United States
GCP
Good Clinical Practice
GSK
GlaxoSmithKline 
GSM
Global Study Manager
HCII
Hybrid Capture II 
HPV
Human papillomavirus
HR
High-risk
HR-HPV
High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 
35, 39, 45, 51, 52, 56, 58, 59, 66 and 68
HSIL
High grade squamous intraepithelial lesion
IB
Investigator Brochure.
ICF
Informed Consent Form
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
 
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IND
Investigational New Drug
IRB
Institutional Review Board
LBC
Liquid Based Cytology
LEEP
Loop Electrosurgical Excision Procedure
LR
Low-risk
LSIL
Low grade squamous intraepithelial lesion
MedDRA
Medical Dictionary for Regulatory Activities
RDE
Remote data entry
SAE
Serious Adverse Event.
SPM
Study Procedures Manual.
SOP
Standard Operating Procedure
VAIN
Vaginal Intraepithelial Neoplasia 
VIN
Vulval Intraepithelial Neoplasia
VLP
Virus-like particle
 
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GLOSSARY OF TERMS
Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An AE can therefore be any unfavourable and unintended 
sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For 
marketed medicinal products, this also includes failure to 
produce expected benefits (i.e. lack of efficacy), abuse or 
misuse.
Blinding:
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes.
Conclusion Visit of Study 
HPV-015
Subjects who participated in the HPV-015 study may 
decide to conclude their participation in the HPV-015 
study at Visit 9, Visit 11 or at the last study visit in HPV-
015 planned under protocol amendment 4.
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
Epoch:
An epoch is a well defined part of a protocol that covers a 
set of consecutive time-points. Generally, an epoch is 
self-contained and allows to perform a data analysis to 
address some of the trial objectives (e.g. primary, booster, 
yearly follow-ups,…).
eTrack:
GSK’s tracking tool for clinical trials.
Global Study Manager
An individual assigned by GSK Biologicals Headquarters 
who is responsible for assuring the co-ordination of the 
operational aspects and proper conduct of a clinical study, 
including compliance with International Conference on 
Harmonisation (ICH) Harmonised Tripartite Guideline 
for Good Clinical Practice (GCP) and GSK policies and 
standard operating procedures.
Investigational 
vaccine/product:
(Synonym of 
Investigational Medicinal 
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, 
including a product with a marketing authorisation when 
used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain 
 
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Product)
further information about an approved use. 
Medical Monitor:
An individual medically qualified to assume the 
responsibilities of the sponsor (GSK Biologicals) 
especially in regards to the ethics, clinical safety of a 
study and the assessment of adverse events.
Protocol amendment:
ICH defines a protocol amendment as: ‘A written 
description of a change(s) to or formal clarification of a 
protocol.’ GSK Biologicals further details this to include 
a change to an approved protocol that affects the safety of 
subjects, scope of the investigation, study design, or 
scientific integrity of the study.
Protocol administrative 
change:
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study. 
NB Any change that falls under the definition of a 
protocol amendment (e.g. a change that affects the safety 
of subjects, scope of the investigation, study design, or 
scientific integrity of the study) MUST be prepared as an 
amendment to the protocol. 
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
Subject:
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the product(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Treatment:
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject, 
identified by a unique number, according to the study 
randomisation or treatment allocation.
Treatment number:
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
 
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1.
INTRODUCTION
1.1.
Background
Cervical cancer is the most important manifestation of genital human papillomavirus 
(HPV) infection and is one of the leading causes of cancer mortality in women worldwide 
[Parkin, 2001a; Parkin, 2001b]. Papillomaviruses, members of the papovaviridae family, 
are non-enveloped deoxyribonucleic acid (DNA) viruses which can cause a variety of 
proliferative epithelial lesions in humans, including benign papillomas (warts) and 
invasive cancer [Lowy, 2001; Zur Hausen, 2002]. 
Currently, over 200 different types of HPVs have been recognized. Based on whether 
they infect basal epithelial cells of the skin or the inner lining of tissues, they are 
categorized as cutaneous or mucosal types [Burd, 2003]. At least 30 HPV types have 
been identified that infect the genital mucosa [Bosch, 1995]. HPV types are also 
classified by their relative malignant potential into low-risk (LR) types (e.g. HPV-6, -11, 
-42, -43, and -44) and high-risk (HR) or oncogenic types (e.g. HPV-16, -18, -31, -33, -34, 
-35, -39, -45, -51, -52, -56, -58, -59, -66, -68 and -70) [Burd, 2003]. Persistent infection 
with an oncogenic HPV type has been clearly associated with the development of 
cervical cancer [Schiffman, 2005] and the association between cervical cancer and 
infection with a HR HPV type is supported both by strong epidemiological evidence and 
the detection of HPV DNA in up to 99.7% of cervical cancers worldwide [Schiffman,
2005; Burd, 2003].
The distribution of HPV types varies within countries and between regions. HPV-16 and 
HPV-18 are the first and second most common types in all regions, with some variation 
in their distribution. HPV-16 is the most prevalent oncogenic HPV type and is present in 
approximately 54% of cervical tumor specimens worldwide. HPV-18 is associated with 
approximately 17% of cervical cancers, with the remaining tumors containing DNA from 
other oncogenic HPV types such as HPV-45 and -31. In combination, these two HPV 
types (HPV-16 and HPV-18) account for approximately 70% of cervical cancer cases 
globally [Clifford, 2003].
In the general population, the estimated worldwide prevalence of HPV among women is 
between 5% and 40% [Baseman, 2005; Franco, 1999]. This wide variation reflects 
underlying population characteristics (i.e. age range, geographic area, risk behaviours), 
the use of different HPV DNA test methods, and also differences in the sexual activity of 
the individuals studied. Assuming a conservative prevalence of 10% in developed 
countries and 15% in developing countries, one author estimated 270 million HPV 
infections amongst women globally [Bosch, 2002].
GlaxoSmithKline (GSK) Biologicals has developed a candidate prophylactic HPV 
vaccine based on L1 proteins of HPV-16 and HPV-18 formulated with AS04 (comprised 
of aluminium hydroxide [Al(OH)3] and 3-O-desacyl-4’-monophosphoryl lipid A [MPL]). 
The vaccine contains HPV-16 and HPV-18 L1 VLP proteins produced using an 
expression system based on the use of insect cells and recombinant Baculoviruses 
encoding L1 proteins of HPV-16 and HPV-18. The recombinant expressed proteins 
 
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undergo self-assembly to form empty viral capsids referred to as virus-like particles 
(VLPs) [Kirnbauer, 1992]. A study comparing different vaccine formulations 
demonstrated that the highest antibody titres were induced by AS04-adjuvanted vaccine 
formulations [Giannini, 2006]. The AS04 adjuvant system is comprised of aluminium 
salts (Al(OH)3) and 3-O-desacyl-4’-monophosphoryl lipid A (MPL) and is also used in 
other vaccines, including a hepatitis B vaccine licensed in Europe for use in 
haemodialysis patients from the age of 15 years and above under the name Fendrix as 
well as in an investigational HSV vaccine.
To date, more than 60 000 adolescent and adult females aged 10 years and above have 
received at least one dose of the HPV vaccine in clinical studies. A pooled safety analysis 
of data from almost 30 000 adolescent and adult females aged 10 years and above, of 
whom 16 142 received at least one dose of HPV vaccine, showed the vaccine to be
generally well tolerated in women of all ages [Descamps , 2009].
Results of a large multinational phase III trial in women aged 15-25 years demonstrated 
high vaccine efficacy against cervical intraepithelial neoplasia grade 2 and above 
(CIN2+), CIN1+ and persistent infection (6-month and 12-month definition) associated 
with HPV-16 and/or HPV-18, significant vaccine efficacy against CIN2+ and CIN3+ 
irrespective of HPV type in the lesion as well as evidence of protection against HPV 
types 31, 33 and 45 [Paavonen, 2009]. This study also demonstrated the vaccine to be 
generally well tolerated in a broad range of women including those of different 
nationalities and ethnicities [Paavonen, 2007].
A long-term efficacy follow-up study in women aged 15-25 years at the time of first 
vaccination demonstrated high vaccine efficacy against incident and persistent HPV-
16/18 infections and their associated cytological cervical lesions up to 6.4 years of 
follow-up [Gall, 2007; Harper, 2004; Harper, 2006; Harper, 2008]. When tested in young 
female adolescents, the vaccine induced immune responses that were approximately 2-
fold higher than those elicited in women 15-25 years of age [Pedersen, 2007]. In women 
up to 55 years of age, the vaccine induced sustained HPV antibody levels up to Month 24
after the first vaccine dose and these antibody levels remained significantly higher than 
those seen after natural infection [Schwarz, 2009].
The vaccine is marketed under the trade name Cervarix™. The first major market in 
which the vaccine was licensed, is Australia, where licensure was obtained in May 2007 
for use in 10 to 45 year old females. In September 2007, the vaccine was licensed in the 
European Union for the prevention of high-grade cervical intraepithelial neoplasia (CIN 
grades 2 and 3) and cervical cancer causally related to HPV types 16 and 18. The present 
indication of the vaccine is for active immunization of girls and women from 10 years of 
age onwards for the prevention of persistent human papillomavirus (HPV) infections and 
related clinical outcomes (cytological abnormalities, pre-cancerous lesions and cervical 
cancer) caused by oncogenic HPV types 16 and 18. In October 2009, Cervarix was also
approved by the United States Food and Drug Administration (US FDA) for use in 
females 10 through 25 years of age. The vaccine is currently licensed in over 100
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Please refer to the current Investigator Brochure for a review of the pre-clinical and 
clinical studies, and the potential risks and benefits of the HPV-16/18 LI VLP AS04 
vaccine.
1.2.
Rationale for the study and study design
This study will be conducted to allow for a safe exit from the HPV-015 study, ensuring 
that women who are at risk of developing a gynaecological lesion are medically 
monitored.
Study subjects enrolled in the control arm of HPV-015 study may have been infected 
with the HPV types included in the vaccine during the study. All subjects may have been 
exposed to other high-risk HPV types. 
The current study will provide annual oncogenic HPV DNA testing and cervical cytology 
examination for a subset of HPV-015 subjects, who at their concluding HPV-015 study 
visit: 

displayed normal cervical cytology but tested positive for oncogenic HPV 
infection

were pregnant so that no cervical sample could be collected 
For eligible subjects, the duration of this gynaecological follow-up will be up to a
maximum of four years after the subjects’ concluding HPV-015 study visit, since most 
cervical lesions develop within four years of infection and most oncogenic HPV 
infections are estimated to clear within two years [Trottier, 2008].
If very few subjects are eligible for this study at one HPV-015 study site and if adequate 
gynaecological follow-up care is available through the local health care system, these 
subjects may be referred to the local health care system, provided that ethical committee 
approval is obtained by the responsible investigator.
The initial protocol of the HPV-015 trial included a three year efficacy follow-up. The 
HPV-015 protocol amendment 3 and 4 extended the HPV-015 trial by one and up to a 
maximum of three additional years, respectively. Subjects may however decide to 
conclude their participation in the HPV-015 study at Visit 9, Visit 11 or at the last study 
visit in HPV-015 planned under protocol amendment 4.
Note that subjects enrolled in this study can also concurrently participate in a GSK 
Biologicals study to receive cross-over vaccination.
This study is not intended to collect long-term efficacy, immunogenicity or safety follow-
up data. Long-term data for GSK Biologicals’ HPV vaccine will be obtained through 
other studies.
1.2.1.
Rationale for the use of placebo
Not applicable.
 
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2.
STUDY OBJECTIVES

To provide clinical management and, if required, treatment to subjects who at their 
concluding HPV-015 study visit displayed normal cervical cytology but tested 
positive for oncogenic HPV infection or who were pregnant at their concluding visit 
of the HPV-015 study so that no cervical sample could be collected
Refer to Section 10.1 for the definition of the study endpoints.
3.
STUDY DESIGN OVERVIEW
An overview of the study design is presented in Figure 1.
Figure 1
Study visits and study procedures
HPV-062 study
HPV-015 study
Concluding HPV-015
visit (Visit 9 or Visit 
11 or Last Visit)
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Study 
Conclusion **
Visit 1
12 months post 
HPV-015 V9/V11/LV
Visit 2
24 months post 
HPV-015 V9/V11/LV
Visit 3
36 months post 
HPV-015 V9/V11/LV
Visit 4
48 months post 
HPV-015 V9/V11/LV
*Subjects with two positive oncogenic HPV DNA tests or one cervical cytology reading ≥ASC-US (atypical squamous 
cells of undetermined significance) positive for oncogenic HPV DNA or one cervical cytology reading ≥LSIL (low grade 
squamous intraepithelial lesion) will be referred for colposcopy evaluation according to the clinical management 
algorithm. Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological samples.
** Study conclusion, see dotted line (--), will occur after any given visit that required treatment of cytological 
abnormality, any given visit with a negative oncogenic HPV DNA test and normal cervical cytology or the closing of 
study activities related to Visit 4.

Experimental design: A phase IIIb, open, multi-centre study with one group.

Treatment allocation: None. 

Blinding: Open.

HPV-015 concluding visit: Subjects who participated in the HPV-015 study may 
decide to conclude their participation in the HPV-015 study at Visit 9, Visit 11 or at 
the last study visit in HPV-015 planned under protocol amendment 4.
 
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
Treatment groups: One study group consisting of a subset of HPV-015 subjects 
who at their concluding HPV-015 study visit:

displayed normal cervical cytology but tested positive for oncogenic HPV 
infection 

were pregnant so that no cervical sample could be collected at that visit
The study eligibility algorithm is presented in Figure 2.
Figure 2
HPV-062 EXT:015 study eligibility algorithm
No cervical sample collected 
due to pregnancy
HPV-015 concluding 
visit completed
Cervical cytology 
test normal
Cervical cytology 
test abnormal
Oncogenic HPV 
DNA test (PCR) 
test positive
Oncogenic HPV 
DNA test (PCR) 
test negative
HPV-015 colposcopy 
and, if required, 
treatment 
No follow-up
HPV-015 study end
Enrol in HPV-062
HPV-015 study end

Vaccination schedule(s): None.

Control: None.

Type of study: Gynaecological follow-up extension study of a subset of HPV-015 
study subjects.

Data collection: Remote Data Entry (RDE).

Duration of the study: Maximum of four years for each subject.

Study visits per subject: Up to four scheduled visits at approximately Months 12, 
24, 36 and 48 after each subject’s concluding HPV-015 study visit. 
Subjects are eligible to join the study at any visit.

Study procedures:
Subjects will enter the study approximately one year after their HPV-015 concluding 
visit. Annual visits will be scheduled for a maximum study duration of
approximately four years.
At each visit, a gynaecological examination will be performed and cervical liquid-
based cytology samples will be collected for cervical cytology examination and 
oncogenic HPV DNA testing, if the cytology reading is normal or ASCUS.
The presence of oncogenic HPV infection will be determined by the Hybrid 
Capture® II (HCII) test, which detects HPV DNA types 16, 18, 31, 33, 35, 39, 45, 
 
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51, 52, 56, 58, 59 and 68 [Vernick, 2003, Digene Corporation 2002]. Cervical 
cytology examination will be performed using the ThinPrep®Pap test.
Continued study participation as well as further referral/treatment will be based on 
the test results from each visit, and will be aligned with the clinical management 
algorithm which is aligned with the 2009 American Society for Colposcopy and 
Cervical Pathology (ASCCP) guidelines for use of HPV DNA testing as an adjunct 
to cytology for cervical cancer screening in women 30 years or older.
The following clinical management algorithm will be applied, refer to Figure 3.

Subjects with normal cervical cytology and who are oncogenic HPV DNA 
negative, will end their participation in the study.

Subjects with normal cervical cytology, but who are oncogenic HPV DNA 
positive in one single test, will be asked to return at the next study visit.
This outcome will only be applicable to subjects who were pregnant at their
concluding HPV-015 study visit so that no cervical sample could be collected at 
that visit.

Subjects with normal cervical cytology, but who are oncogenic HPV DNA 
positive in two subsequent tests, will be referred to colposcopy. The result of the 
subjects’ last HPV-015 study visit will be taken into account at Visit 1.

Subjects with a single cervical cytology reading of ASC-US (atypical 
squamous cells of undetermined significance) positive for oncogenic HPV DNA 
will be referred to colposcopy.

Subjects with a single cervical cytology reading of LSIL (low grade squamous 
intraepithelial lesion) will be referred to colposcopy.
Please note that a missing result for HCII will be managed as oncogenic HPV 
positive.
In case of referral for colposcopy, the post-colposcopy follow-up strategies are:

If no lesion is detected or the detected lesion does not require any treatment, 
subjects will be asked to return at the next study visit.

If a lesion that requires treatment is detected, the subject should be referred to 
treatment according to local medical practice. Any further management 
following local cervical therapy for cervical lesions will be handled according to 
local medical practice within the local health care system. After treatment, the 
subject’s participation in the study will end.
As management algorithms cannot define every clinical situation, it is the
investigator’s (or his/her designee’s) responsibility to exercise appropriate clinical 
judgement in the medical management of each individual case.
Once their study participation ends, all subjects should be referred to their local 
health care system. 
Subjects who have not developed cervical lesions by the end of the study, but who 
are still positive for oncogenic HPV infection, should be informed of the potential 
 
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risks of being positive for oncogenic HPV DNA, and the importance of continued 
follow-up.
Figure 3
Clinical management algorithm
HPV-062 Visit1, 2, 3 and 4
Cervical cytology examinationand oncogenic HPV test (HCII), if applicable$
Normal cervical cytology /
HCII negative
OR
ASC-US / HCIInegative
Normal cervical cytology / 
HCII positive
≥ASC-US / HCII positive
OR
≥LSIL 
First time: nextstudyvisit
Second time: colposcopy *
Colposcopy **
No lesion
OR
No lesionrequiringtreatment
Lesionrequiringtreatment
Treatmentaccording
to local practice
Studyconclusion
Return to nextstudyvisit
After Visit4
Studyconclusion
Studyconclusion
HPVDNA test (HCII) = Hybrid Capture® II test detecting HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.
Specimens will be reported as “Quantity Not Sufficient” (QNS) in the case where there is an inadequate amount of cells for HCII and 
preferentially, a repeat sample will be collected. Missing HCII test results should be managed as oncogenic HPV positive
* = The result of the subject’s concluding HPV-015 study visit will be taken into account. Subjects who were pregnant at that visit so 
that no cervical sample could be collected, and who display normal cytology but are positive for oncogenic HPV DNA at Visit 1, will 
return for the next study visit.
** = Colposcopy and/or colposcopy-directed biopsies will be performed according to local medical practice.
$ = Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological samples.

Study visit activities and gynaecological follow-up reporting

Gynaecological examination at Visit 1, Visit 2, Visit 3 and Visit 4.

Collection of cervical liquid-based cytology samples at Visit 1, Visit 2, Visit 3 
and Visit 4 for cervical cytology examination and oncogenic HPV DNA testing, 
if the cytology reading is normal or ASCUS.

Referral to colposcopy according to protocol clinical management algorithm, if 
required.

Conduct of colposcopy, colposcopy directed biopsies and local cervical therapy 
according to local medical practice, if required.

Recording of colposcopic referral according to management algorithm, if 
required.
 
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
Recording of treatment referrals according to local medical practice, if required.

Safety reporting:

All fatal SAEs will be reported.

All SAEs assessed as being possibly related to study participation will be 
reported.

All SAEs assessed as being possibly related to a concurrent GSK medication
will be reported.

Withdrawal from the study due to adverse events (AEs) or SAEs will be 
reported.
No other AEs or SAEs for HPV-015 study subjects will be reported in this study. AEs 
and SAEs related to the vaccine administrated in the HPV-015 trial should be reported as 
part of the HPV-015 study, as described in the HPV-015 study protocol.
4.
STUDY COHORT
4.1.
Number of subjects
The study population will contain a subset of HPV-015 study subjects who displayed 
normal cervical cytology but tested positive for oncogenic HPV infection at their 
concluding HPV-015 study visit. Additionally, subjects who were pregnant at their 
concluding study visit were not able to provide a cervical sample and are therefore 
eligible for the study.
In total, approximately 1500 HPV-015 study subjects are expected to be eligible to 
participate in this study.
4.2.
Inclusion criteria
All subjects must satisfy ALL the following criteria at study entry:

Written informed consent obtained from the subject prior to enrolment.

Subjects who the investigator believes that they can and will comply with the 
requirements of the protocol.

A subject previously enrolled in the study HPV-015 and who fulfils either of the 
following criteria:

displayed normal cervical cytology but tested positive for oncogenic HPV 
infection at her concluding HPV-015 study visit 

was pregnant so that no cervical sample could be collected at her concluding 
HPV-015 study visit
 
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4.3.
Exclusion criteria for enrolment
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:

A subject who at the HPV-015 concluding study visit displayed normal cervical 
cytology and who was negative for oncogenic HPV infection at that visit.

A subject who at the HPV-015 concluding study visit had a cervical lesion at that 
visit or who had a cervical lesion that required treatment at her HPV-015 exit 
colposcopy.

A subject for whom the cervical cytology results from the concluding HPV-015 
study visit were unavailable for reasons other than pregnancy.
If at the time of enrolment the subject experiences heavy bleeding (menstruation or other) 
or heavy vaginal discharge, the pelvic exam cannot be performed. Enrolment will be 
deferred until condition is resolved according to investigator’s medical judgment.
If the subject is pregnant at the time of enrolment, enrolment should be deferred until at 
least 3 months after the pregnancy has been completed. The subject should attend the 
next protocol scheduled visit (i.e. within the protocol windows). Subjects are eligible to 
enter the study at any visit.
5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the 
informed consent process
GSK will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable country-specific regulatory 
requirements, prior to a site initiating the study in that country.
The study will be conducted in accordance with all applicable regulatory requirements, 
including a United States Investigational New Drug Application (US IND).
The study will also be conducted in accordance with the ICH Guideline for Good Clinical 
Practice (GCP) all applicable subject privacy requirements and the guiding principles of 
the Declaration of Helsinki. 
Conduct of the study includes, but is not limited to, the following:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject informed consent.

Investigator reporting requirements as stated in the protocol.
GSK will provide full details of the above procedures to the investigator, either verbally, 
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Freely given and written informed consent must be obtained from each subject prior to 
participation in the study.
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgement, local regulations and requirements should guide the final 
structure and content of the local version of the ICF. 
The investigator has the final responsibility for the final presentation of the ICF, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to 
GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC.
5.2.
Subject identification and randomisation of treatment
5.2.1.
Subject identification (Administrative change 1)
Subjects will retain their identification numbers from study HPV-015.
A new identification number will be assigned to the subject to preserve the blind for 
HPV-015 data during this HPV-015 extension study.
5.2.2.
Randomisation of treatment
Not applicable.
5.2.3.
Randomisation of subjects to assay subsets 
Not applicable.
5.3.
Method of blinding 
Not applicable.
5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM). The SPM provides the 
investigator and the site personnel with administrative and detailed technical information 
that does not impact the safety of the subjects.
 
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5.4.1.
Cytology Report Terminology
Liquid-based cytology tests and oncogenic HPV tests (HCII) will be performed at Quest 
Diagnostics (Teterboro, NJ, US) or another GSK designated laboratory. Each 
cytopathological specimen will be reported according to the Bethesda 2001 Classification 
of cytological findings [Wright, 2002]. The terminology will include a statement as to 
whether a specimen is satisfactory or unsatisfactory.
The following categories for cytology reading will be specified:

Negative for intraepithelial lesion or malignancy (negative).

Negative/HCII negative (Normal/oncogenic HPV negative)

Negative/HCII positive (Normal/oncogenic HPV positive).

Negative/HCII quantity not sufficient (Normal/QNS).

Unsatisfactory.

Atypical squamous cells of undetermined significance (ASC-US).

ASC-US/HCII negative (ASC-US/oncogenic HPV negative)

ASC-US/HCII positive (ASC-US/oncogenic HPV positive).

ASC-US/HCII quantity not sufficient (ASC-US/QNS).

Atypical squamous cells cannot exclude HSIL (ASC-H).

Low-grade squamous intraepithelial lesion (LSIL).

High-grade squamous intraepithelial lesion (HSIL).

Atypical glandular cells (AGC).

Invasive malignancy.
Specimens will be reported as “Quantity Not Sufficient” (QNS) in the case where there is 
an inadequate amount of cells for HCII and preferentially, a repeat sample will be 
collected. Missing HCII test results should be managed as oncogenic HPV positive.
Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological 
samples.
The results of the cytology and HCII testing will be communicated to the investigator (or 
his/her designee) by Quest Diagnostics (Teterboro, NJ, US), or another GSK designated 
laboratory. The investigator (or his/her designee) will notify the subject of the test result 
and if applicable, it is recommended that the subject should receive colposcopy within 30 
days after cytology and HCII results have been communicated by Quest Diagnostics
(Teterboro, NJ, US), or another GSK designated laboratory.
 
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5.4.2.
Histopathology Report Terminology
Any histopathological lesions will be biopsied or excised locally according to local 
medical practice. Histopathological reports on biopsy and excision specimens will be 
written according to local medical practice. 
5.4.3.
Clinical Management Algorithm
The clinical management algorithm in Figure 3 describes the management of all cytology 
results obtained at study visits. 
5.4.4.
Unsatisfactory cytological findings
When the laboratory results deem a cervical liquid-based cytology specimen 
“unsatisfactory”, study personnel are required to repeat the specimen as soon as possible 
after cytology results have been communicated and not wait until the next scheduled 
protocol visit. Only satisfactory results of a repeat cytology result will count as the final 
cytology result for that study visit. 
In addition, cytological specimens reported as “satisfactory for evaluation-endocervical/ 
transformation zone component absent” should be managed according to the given
cytological diagnosis. These smears should not be repeated but the information may be 
used for quality control monitoring.
Missing cytology results will be recorded as “missing results” (in the case of lost/ 
damaged sample) and preferentially a repeat cytology will be performed.
Specimens will be reported as “Quantity Not Sufficient” (QNS) in the case where there is 
an inadequate amount of cells for HCII and preferentially, a repeat sample will be 
collected. Missing HCII test results should be managed as oncogenic HPV positive 
according to the requirements specified in the clinical management algorithm (refer to 
Figure 3).
5.4.5.
Abnormal cytology
Observation of abnormal cytology ASC-US (atypical squamous cells of undetermined 
significance) positive for oncogenic HPV DNA as determined by the HCII test will result 
in referral to colposcopic evaluation.
Observation of LSIL (low grade squamous intraepithelial lesion) will result in referral 
to colposcopic evaluation.
5.5.
Colposcopic evaluation
The clinical management algorithm in Figure 3 describes the management of all cytology 
results obtained at study visits. 
 
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Colposcopy will be performed according to local medical practice. All colposcopies will
be recorded in the eCRF and every attempt will be made to document colposcopy 
performed outside the study in the specific section on the eCRF.
Any cervical lesions will be biopsied or excised according to local medical practice. In 
addition, the vagina and vulva may be inspected with each colposcopy. All tissue will be 
processed locally.
5.6.
Management of cervical lesions
Local cervical therapy for cervical lesions will be handled locally according to local 
medical practice. 
Any further management following local cervical therapy for cervical lesions will be 
handled according to local medical practice within the local health care system. The 
treatment of cervical, lesions (or other lesions detected during the medical evaluation 
such as vaginal or vulval lesions) is to be handled according to local medical practice.
5.7.
Outline of study procedures
Table 1 presents the outline of the study procedures to be followed by the investigator (at 
the study centre).
Subjects are eligible to enter the study at any visit.
The intervals between visits are outlined in Table 2. It is the investigator’s responsibility 
to ensure that the intervals between visits are followed as closely as possible. If a subject 
misses a visit, the missed visit will not be performed, but the subject may return to the 
next scheduled visit.
If a subject becomes pregnant during the study, she will not undergo any gynaecological 
examination nor have a cervical cytology sample taken during her pregnancy. The missed 
visit will not be performed. Three months after delivery, the subject may return to the 
next scheduled visit. For subject that are pregnant at the last study visit, no conclusion 
visit will be performed. Women should be informed of the potential risks of being 
positive for oncogenic HPV DNA and of the importance of continued follow-up.
Investigators will follow-up subjects with SAEs assessed as being related to study 
procedures or SAEs assessed as being related to a concurrent GSK medication until the 
event has resolved, subsided, stabilised, disappeared, the event is otherwise explained, or 
the subject is lost to follow-up, or, in the case of non-serious AEs leading to study 
withdrawal, until they are lost to follow-up.
 
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Table 1
List of study procedures
Visit
VISIT 1
VISIT 2
VISIT 3
VISIT 4
Timing (Months post concluding HPV-015 visit 
(Visit 9, Visit 11 or last HPV-015 study visit as 
planned in the HPV-015 protocol amendment 4))
Month 12
Month 24
Month 36
Month 48
Informed consent

*
*
*
Check inclusion criteria

*
*
*
Check exclusion criteria

*
*
*
Collect demographic data

*
*
*
Gynaecological examination




Collect cervical liquid-based cytology sample




Review oncogenic HPV infection status, if 
applicable
○
○
○
○
Review cervical cytology status
○
○
○
○
Record referral to colposcopy, if applicable




Record treatment referral, if applicable




Record concomitant medication/vaccination, if 
applicable




Review continued study participation and counsel 
subjects for gynaecological follow-up if study 
conclusion.$
○
○
○
Reporting of fatal SAEs




Reporting of SAEs related to study participation




Reporting of SAEs related to a concurrent GSK 
medication




Reporting of AEs and SAEs leading to study 
withdrawal




Study Conclusion
$
$
$

is used to indicate a study procedure that requires documentation in the individual eCRF.
○ is used to indicate a study procedure that does not requires documentation in the individual eCRF.
*Subjects are eligible to join the study at any visit
$ A subject who has been referred to local treatment or who displays normal cervical cytology and who tests negative 
for oncogenic HPV DNA  will exit the study.
Table 2
Intervals between study visits
Interval (Months after HPV-015 concluding visit (Visit 9,
Visit 11 or last HPV-015 study visit as planned in the 
HPV-015 protocol amendment 4))
Length of 
interval (days)
Recommended interval 
between scheduled visits 
(days)*
Concluding visit HPV-015 Visit 1 HPV-062 (Month 12)
183-547
365
Concluding visit HPV-015 Visit 2 HPV-062 (Month 24)
548-912
730
Concluding visit HPV-015 Visit 3 HPV-062 (Month 36)
913-1277
1095
Concluding visit HPV-015 Visit 4 HPV-062 (Month 48)
1278-1642
1460
*There should be a minimum of 183 days between two consecutive study visits.
5.8.
Detailed description of study procedures
Subjects are eligible to join the study at any visit.
 
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5.8.1.
Procedures prior to study participation
5.8.1.1.
Informed consent
Before performing any other study procedure, the signed informed consent of the subject 
needs to be obtained. Refer to Section 5.1 for information on how to obtain informed 
consent.
5.8.2.
Procedures during study participation
5.8.2.1.
Check inclusion and exclusion criteria
Check all applicable inclusion and exclusion criteria as described in Sections 4.2 and 4.3
before enrolment. 
If a subject is enrolled while not meeting all inclusion criteria or while meeting any of the 
exclusion criteria, this must be reported in the eCRF.
5.8.2.2.
Collect demographic data
Record demographic data such as age and gender in the subject’s eCRF. 
5.8.2.3.
Gynaecological examination
Perform gynaecological examination according to local medical practice. This may 
include breast exam. Treatment of any abnormality observed during this examination will 
be performed according to local medical practice or by referral to an appropriate health 
care provider. Study related pelvic exams for collection of cervical specimens will be 
suspended in women known to be pregnant and will resume 3 months after resolution. 
Missing procedures will not be rescheduled.
5.8.2.4.
Cervical sampling

Collect sample for cervical liquid-based cytology examination (ThinPrep® PapTest).
Oncogenic HPV DNA (HCII) testing will be performed, if applicable.
Sexual intercourse should be avoided for the 24 hours before collection of a cervical 
specimen. Cervical specimen collection must be performed a minimum of one day 
after menstrual flow has ceased. Female subjects who will be menstruating during 
planned visits will be invited to reschedule cervical specimen collection and/or their 
pelvic examination according to the medical judgement of the investigator. Pelvic 
examinations for collection of cervical specimens will be suspended in female 
subjects known to be pregnant until 3 months after resolution.
In case of abnormal cytological findings and if contact cannot be confirmed by phone, a 
certified/registered letter requiring the signature of the subject will be sent by the study 
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5.8.2.5.
Review oncogenic HPV infection status and cervical cytology status

Review oncogenic HPV infection status, if applicable.

Review cervical cytology status.
5.8.2.6.
Recording of referral to colposcopy and treatment (if applicable)

Record referral for colposcopy according to clinical management algorithm, if 
applicable. The result of the subjects’ last HPV-015 study visit will be taken into 
account. It is recommended that colposcopy is performed within 30 days of referral.

Record treatment referral, if applicable.
5.8.2.7.
Recording of concomitant medication

Record concomitant medication, if applicable.
5.8.2.8.
Review of continued study participation

Review continued participation in study according to clinical management algorithm 
and counsel the subject for appropriate continuous gynaecological follow up if study 
conclusion.
5.8.2.9.
Reporting of non-serious AEs and SAEs

Report all fatal SAEs (refer to Section 8.1.3 for the definition of SAEs).

Report all SAEs assessed as being possibly related to study participation.

Report all SAEs assessed as being possibly related to a concurrent GSK medication.

Report all AEs/SAEs (refer to Section 8.1 for the definition of AEs) leading to 
withdrawal from the study.
Refer to Section 8.3 for procedures for the Investigator to record AEs and SAEs that are 
related to study participation or GSK concomitant medication/vaccination and to Section 
8.4 for guidelines on how to report these AEs/SAEs to GSK Biologicals.
The subjects will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious. 
5.8.2.10.
Study conclusion
At study conclusion, the subject will be counselled for appropriate continuous 
gynaecological follow up. No other post-study treatment will be provided.
5.9.
Biological Sample handling and analysis
Please refer to the SPM for details of biospecimen management (handling, storage and 
shipment).
 
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Samples will not be labelled with information that directly identifies the subjects but will 
be coded with the identification number for the subject (subject number). 
Collected samples may be used in other assays, for test improvement or test development 
of analytical methods related to the study vaccine and its constituents or the disease under 
study to allow to achieve a more reliable measurement of the vaccine response. Under 
these circumstances, additional testing on the samples may be performed by GSK 
Biologicals outside the scope of this protocol. 
Refer to the GSK Biologicals Research & Development Position Paper which describes 
the rationale for and some examples of what further investigations may include.
Any sample testing will be done in line with the consent of the individual subject. 
Any human pharmacogenetic testing will require specific consent from the individual 
subjects and the ethics committee approval. Any anti-HIV testing will also require 
specific consent and ethics committee approval.
Refer also to the Investigator Agreement, where it is noted that the Investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s).
Collected samples will be stored for up to 15 years (counting from when the last subject 
performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK Biologicals.
5.9.1.
Use of specified study materials
When materials are provided by GSK Biologicals or Quest Diagnostics, it is 
MANDATORY that all clinical samples be collected and stored exclusively using those 
materials in the appropriate manner. The investigator must ensure that his/her personnel 
and the laboratory(ies) under his/her supervision comply with this requirement. However, 
when GSK Biologicals or Quest Diagnostics does not provide material for collecting and 
storing clinical samples, then appropriate materials from the investigator’s site are to be 
used. Refer to the module of clinical trial supplies in the SPM.
5.9.2.
Biological samples
Table 3
Biological samples
Sample type
Quantity
Unit
Timepoint
Subset /Sub-cohort Name
Cervical sample
N/A
N/A
scheduled
N/A
5.9.3.
Laboratory assays
Please refer to Section 5.9.4 for a detailed description of the assays performed in the 
study.
 
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The following sections describe laboratory assays to be used for all biological samples 
collected throughout the entire study period. Detailed instructions for all laboratory 
assays will be provided in a separate manual to the investigator. 
Cytology samples will be shipped to Quest Diagnostics (Teterboro, NJ, US), or another 
GSK designated laboratory (refer to Appendix A) prior to any laboratory assay/testing 
being performed.
Biopsy samples will be processed locally, if applicable.
The GSK Biologicals’ clinical laboratories have established a Quality System supported 
by procedures. The activities of GSK Biologicals’ clinical laboratories are audited
regularly for quality assessment by an internal (sponsor-dependent) but laboratory-
independent Quality Department.
Sample analysis will be performed in the specific laboratories described in Table 4.
Table 4
Laboratory assays
Laboratory
Discipline
Component
Scale
Method
Test kit/
Manufacturer
Unit
Cut-
off
Laboratory*
Qualitative
cervical
cytology
Bethesda 
2001 System 
for reporting 
cervical 
Cytology 
diagnoses
Qualitative
Microscopy 
of cervical
cytology
ThinPrep®PapTest™/ 
Cytyc Corp.
N/A
N/A
Quest 
Diagnostics 
(Teterboro, NJ 
US) or another 
GSK 
designated 
laboratory
Qualitative
DNA
hybridisation
HPV-16, 18, 
31, 33, 35, 39, 
45, 51, 52, 56, 
58, 59 and 68 
(Oncogenic 
probe 
[cocktail B])
Qualitative
Nucleic acid 
hybridisation
Hybrid Capture® II
HPV DNA 
Test/Digene 
Corporation
N/A
N/A
Quest 
Diagnostics 
(Teterboro, NJ 
USA) or 
another GSK 
designated 
laboratory
*GSK Biologicals laboratory or validated laboratory designated by GSK Biologicals.
N/A: Not Applicable
Collected samples will be used for purposes related to the quality assurance of data 
generated within the scope of this protocol, such as for maintenance of assays described 
in this protocol and comparison between analytical methods and/or laboratories.
5.9.4.
Biological samples evaluation
5.9.4.1.
Cytology
Cervical cytology will be performed using the ThinPrep® PapTest (Cytyc Corporation, 
Boxborough, MA, USA), by Quest Diagnostics (Teterboro, NJ, US), or another GSK 
designated laboratory. Cervical cells for ThinPrep® cytology will be collected using the 
sampling device provided and rinsed into a collection vial containing PreservCyt® 
medium (provided by GSK Biologicals or Quest Diagnostics).
 
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Note that collection of cytological specimens at colposcopy will be performed according 
to local medical practice.
5.9.4.2.
HPV DNA Testing by Hybrid Capture II (HCII)
After ThinPrep® cytology slides have been prepared, residual PreservCyt® specimens on 
slides read as normal or ASCUS will be tested for HPV DNA. Testing will be done by 
Quest Diagnostics (Teterboro, NJ, US), or another GSK designated laboratory using the 
Hybrid Capture® II test (HCII; Digene Corp., Gaithersburg, MD, USA). Probe B will be 
used and is designed to detect infections with one of 13 oncogenic HPV types (HPV 
types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) [Vernick 2003, Digene 
Corporation 2002]. This test does not provide type-specific data.
5.9.5.
Immunological correlates of protection
No correlate of protection has been demonstrated for the HPV-16 and HPV-18 antigens 
used as part of the HPV-16/18 L1 VLP AS04 vaccine.
6.
STUDY VACCINE AND ADMINISTRATION
No investigational product will be administered in the current study.
GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine was administered to the HPV-015 
study vaccine group. Cross-over vaccination will be offered to the subjects in the HPV-
015 control group either by providing commercially available HPV-16/18 L1 VLP AS04 
vaccine or, if the vaccine is not licensed for the respective age group in the considered 
country, through a separate clinical trial protocol. No vaccine will be administered in the 
current study.
6.1.
Concomitant medication/vaccination
At each study visit, the investigator should question the subject about any medication 
taken and vaccination received by the subject.
All concomitant medication administered for the treatment of an AE that leads to study 
withdrawal must be recorded in the eCRF with generic name of the medication (trade 
names are allowed for combination drugs only), medical indication (including which 
AE), total daily dose, route of administration, start and end dates of treatment.
Similarly, concomitant medication administered for the treatment of an ultimately fatal 
SAE, an SAE leading to study withdrawal, an SAE related to study participation or an 
SAE related to GSK products at any time, must be recorded on the SAE screens in the 
eCRF, as applicable. Refer to Section 8.1.3 for the definition of a SAE.
Any investigational medication or vaccine must be recorded in the eCRF.
 
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6.1.1.
Time window for recording concomitant medication/vaccination
in the eCRF
Concomitant medication/vaccination as defined in Section 6.1 as well as investigational 
medication or vaccine administered from the concluding visit of HPV-015 to the HPV-
062 EXT:015 study conclusion must be recorded in the eCRF throughout the study 
period.
7.
HEALTH ECONOMICS
Not applicable.
8.
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
The investigator or site staff is/are responsible during the study for the detection and 
documentation of events meeting the criteria and definition of an adverse event (AE) or 
serious adverse event (SAE) as provided in this protocol.
Each subject will be instructed to contact the investigator immediately should they
manifest any signs or symptoms they perceive as serious.
8.1.
Safety definitions
NOTE: The term AE denotes both non-serious and serious adverse events. In this 
study, only fatal SAEs, SAEs related to study participation, SAEs related to a 
concurrent GSK medication and AEs or SAEs leading to withdrawal from the study 
will be reported.
8.1.1.
Definition of an adverse event
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
Examples of an AE include:

Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
 
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
New conditions detected or diagnosed after investigational product administration 
even though they may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational product or a concurrent medication (overdose per se should not be 
reported as an AE/SAE).

Signs, symptoms temporally associated with vaccine administration.

Significant failure of expected pharmacological or biological action. 
8.1.2.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

For therapeutic studies, the disease/disorder being studied, or expected progression, 
signs, or symptoms of the disease/disorder being studied, unless more severe than 
expected for the subject’s condition.
AEs may include pre- or post-treatment events that occur as a result of protocol-
mandated procedures (i.e. invasive procedures, modification of subject’s previous 
therapeutic regimen).
8.1.3.
Definition of a serious adverse event 
A serious adverse event (SAE) is any untoward medical occurrence that:
a.
Results in death.
b.
Is life-threatening.
NB: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalisation or prolongation of existing hospitalisation.
NB: In general, hospitalisation signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or out-patient setting. Complications that 
occur during hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, the 
AE should be considered serious.
 
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Hospitalisation for elective treatment of a pre-existing condition (known/diagnosed 
prior to informed consent signature) that did not worsen from baseline is NOT
considered an AE.
d.
Results in disability/incapacity, or
NB: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza, and accidental trauma (e.g. sprained ankle) which 
may interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect in the offspring of a study subject.
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalisation.
8.1.4.
Solicited adverse events
Not applicable.
8.1.5.
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events 
Abnormal laboratory findings (e.g. clinical chemistry, haematology, urinalysis) or other 
abnormal assessments that are judged by the investigator to be clinically significant will 
be recorded as AEs or SAEs if they meet the definition of an AE, as defined in Section 
8.1.1 or of a SAE, as defined in Section 8.1.3. Clinically significant abnormal laboratory 
findings or other abnormal assessments that are detected during the study or are present at 
baseline and significantly worsen following the start of the study will be reported as AEs 
or SAEs. However, clinically significant abnormal laboratory findings or other abnormal 
assessments that are associated with the disease being studied, unless judged by the 
investigator as more severe than expected for the subject’s condition, or that are present 
or detected at the start of the study and do not worsen, will not be reported as AEs or 
SAEs.
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
 
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8.2.
Events or outcomes not qualifying as adverse events or 
serious adverse events
8.2.1.
Pregnancy
Pregnancies and pregnancy outcomes during the current study will not be followed-up, if 
they are not fatal SAEs, SAEs related to study participation, SAEs related to a concurrent 
GSK medication or AEs/SAEs leading to withdrawal from the study.
While pregnancy itself is not considered an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or a 
SAE, as described in Sections 8.1.1 and 8.1.3, and will be followed as described in 
Section 8.4.4, if it is a fatal SAE, an SAE related to study participation, an SAE related to 
a concurrent GSK medication or an AE/SAE leading to withdrawal from the study.
A spontaneous abortion is always considered to be a SAE and will be reported as 
described in Section 8.4, if it is a fatal SAE, an SAE related to study participation, an 
SAE related to a concurrent GSK medication or an AE/SAE leading to withdrawal from 
the study. Furthermore, any SAE occurring as a result of a post-study pregnancy AND
considered by the investigator to be reasonably related in time to a study procedure will 
be reported to GSK Biologicals as described in Section 8.4, if it is a fatal SAE, an SAE 
related to study participation, an SAE related to a concurrent GSK medication or an 
AE/SAE leading to withdrawal from the study. While the investigator is not obligated to 
actively seek this information from former study participants, he/she may learn of a 
pregnancy through spontaneous reporting.
Serious pregnancy outcomes that are reported as related to the study vaccine administered 
in HPV-015 have to be reported under the HPV-015 protocol.
8.3.
Detecting and recording adverse events, serious adverse 
events and pregnancies
8.3.1.
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies
In order to fulfil international reporting obligations, SAEs that are related to study 
participation (e.g. protocol-mandated procedures, invasive tests, a change from existing 
therapy) or are related to a concurrent GSK medication or any fatal SAE will be collected 
and recorded from the time the subject consents to participate in the study until she is 
discharged.
All AEs leading to study withdrawal that are either observed by the investigator or one of 
his clinical collaborators or reported by the subject spontaneously or in response to a 
direct question will be evaluated by the investigator. AEs leading to study withdrawal 
that are not previously documented in the study will be recorded in the Adverse Event 
screen within the subject’s eCRF. The nature of each event, date and time (where 
 
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appropriate) of onset, outcome and intensity should be established. Details of any 
corrective treatment should be recorded on the appropriate page of the eCRF.
An overview of the protocol-required reporting periods for adverse events and serious 
adverse events is given in Table 5.
Table 5
Reporting periods for adverse events and serious adverse events
Study activity
Visit 1.
Visit 2
Visit 3
Visit 4
Month 12
Month 
24
Month 
36
Month 48
Reporting of SAEs 
related to study
participation, SAEs 
related to a concurrent 
GSK medication or 
any fatal SAEs,
Reporting of AEs or 
SAE leading to study 
withdrawal
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 5. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a subject has been discharged from the HPV-015 
study, and he/she considers the event reasonably related to the investigational product, 
the investigator will promptly notify the Study Contact for Reporting SAEs. Any post-
study SAEs for HPV-015 subjects are to be recorded in the HPV-015 study.
8.3.2.
Evaluation of adverse events and serious adverse events
8.3.2.1.
Active questioning to detect adverse events and serious adverse 
events
As a consistent method of soliciting AEs, the subject should be asked a non-leading 
question such as:
‘Have you felt different in any way since the previous visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE on the eCRF or SAE Report screens as applicable. It is not acceptable for the 
investigator to send photocopies of the subject’s medical records to GSK Biologicals 
instead of the appropriate completed AE/SAE screens in the eCRF. However, there may 
be instances when copies of medical records for certain cases are requested by GSK 
Biologicals. In this instance, all subject identifiers will be blinded on the copies of the 
medical records prior to submission to GSK Biologicals.
 
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The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
8.3.2.2.
Assessment of adverse events
8.3.2.2.1.
Assessment of intensity
Intensity of the following AEs will be assessed as described:
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all other AEs, i.e. unsolicited symptoms, including SAEs reported during the 
study. The assessment will be based on the investigator’s clinical judgement.
The intensity of each AE and SAE recorded in the eCRF or SAE Report screens as
applicable, should be assigned to one of the following categories:
1 (mild)
=
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2 (moderate)
=
An AE which is sufficiently discomforting to interfere with 
normal everyday activities.
3 (severe)
=
An AE which prevents normal, everyday activities. In 
adults/adolescents, such an AE would, for example, prevent 
attendance at work/school and would necessitate the 
administration of corrective therapy.
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category utilised for rating the intensity of an event; and both AEs and SAEs can 
be assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 8.1.3.
8.3.2.2.2.
Assessment of causality
The investigator should assess the causality of each AE/SAE. The investigator will use 
clinical judgement to determine the relationship of AEs/SAEs to study procedures or to 
GSK concomitant medication. Alternative causes, such as natural history of the 
underlying diseases, concomitant therapy and other risk factors will be considered and 
investigated.
There may be situations when an AE/SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However it is very 
important that the investigator always makes an assessment of causality for every event 
prior to submission of the AE/SAE to GSK Biologicals. The investigator may change 
his/her opinion of causality in light of follow-up information, amending the SAE 
information accordingly. 
 
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If an event meets the criteria to be determined ‘serious’ (refer to Section 8.1.3), it will be 
examined by the investigator to the extent to enable determination of all contributing 
factors applicable to each SAE. 
Possible contributing factors include:

Medical history.

Concomitant medication.

Protocol required procedure.

Other procedure not required by the protocol.

Other cause (specify).
8.3.2.3.
Assessment of outcomes
Outcome of any non-serious AE leading to study withdrawal or any SAE reported during 
the entire study will be assessed as:

Recovered/resolved.

Not recovered/not resolved.

Recovering/resolving.

Recovered with sequelae/resolved with sequelae.

Fatal (SAEs only).
8.4.
Reporting and follow-up of adverse events, serious adverse 
events
8.4.1.
Prompt reporting of serious adverse events to GSK Biologicals
SAEs will be reported promptly to GSK as described in Table 6 once the investigator 
determines that the event meets the protocol definition of an SAE.
Table 6
Time frames for submitting SAEs and other events reports to GSK 
Biologicals
Initial Reports
Follow-up Information 
on a Previous Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours*
SAE report/SAE screen
24 hours*
SAE report/SAE screen
* Time frame allowed after receipt or awareness of the information.
In case the electronic reporting system is temporarily unavailable, a back up system is in 
place. Please refer to Section 8.4.3 for a detailed description. 
Please see the Sponsor Information Sheet for contact details.
 
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Back-up Study Contact for Reporting SAEs
GSK Biologicals Clinical Safety & Pharmacovigilance
Fax: 
 or 
24/24 hour and 7/7 day availability
8.4.2.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.4.1. GSK Biologicals has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational product and unexpected. The 
purpose of the report is to fulfil specific regulatory and Good Clinical Practice (GCP) 
requirements, regarding the product under investigation.
8.4.3.
Completion and transmission of SAEs reports to GSK Biologicals
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator will complete and submit the information in the SAE screens in eCRF within 
24 hours. The SAE screens in eCRF will always be completed as thoroughly as possible 
with all available details of the event and will be submitted by the investigator. If the 
investigator does not have all information regarding an SAE, he/she will not wait to 
receive additional information before notifying GSK of the event and completing the 
SAE screens in eCRF. The SAE screens in eCRF should be updated when additional
relevant information is received WITHIN 24 HOURS.
The investigator will always provide an assessment of causality at the time of the initial 
report.
8.4.3.1.
Back-up system in case the electronic SAE reporting system does not 
work
If the SAE reporting system has been down for 24 hours, the investigator or his/her 
delegate should fax an SAE report form directly to the GSK Central Safety department 
(please refer to Section 8.4.1) within 24 hours. The maximum timeline for reporting 
SAEs to central safety is therefore 48 hours. 
NB. This back-up system should only be used if the electronic reporting system is not 
working and NOT if the system is slow.
As soon as the electronic reporting system is working again, the investigator or delegate 
must update the SAE screens in the eCRF within 24 hours. 
 
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The final valid information for regulatory reporting will be the information reported 
through the electronic system. 
When additional information is received on a SAE after freezing of the subject’s eCRF, 
new or updated information is to be recorded on the paper SAE Report Form, with all 
changes signed and dated by the investigator. The updated SAE Report Form should be 
resent to GSK Biologicals WITHIN 24 HOURS of receipt of the follow-up information.
In rare circumstances, if the electronic system for reporting SAEs does not work and in 
the absence of facsimile equipment, notification by telephone is acceptable, with a copy 
of the SAE Report Form sent by email or by mail. Initial notification via the telephone 
does not replace the need for the investigator to complete and submit SAE screens in the 
eCRF (or complete and sign the SAE Report Form if back-up system needs to be used).
In the event of a death determined by the investigator to be related to vaccination, 
completion of SAE screens in the eCRF/sending of the fax (if electronic SAE reporting 
system does not work or after freezing of the subject’s eCRF) must be accompanied by 
telephone call to the Study Contact for Reporting SAEs.
8.4.4.
Follow-up of adverse events and serious adverse events
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide further information to GSK Biologicals on the subject’s condition.
All SAEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the 
end of the study.
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until the 
end of the study.
Investigators will follow-up subjects:

With SAEs or subjects withdrawn from the study as a result of an AE, until the event 
has resolved, subsided, stabilised, disappeared, or until the event is otherwise 
explained, or the subject is lost to follow-up.
Clinically significant laboratory abnormalities will be followed up until they have 
returned to normal, or a satisfactory explanation has been provided. Additional 
information (including but not limited to laboratory results) relative to the subsequent 
course of such abnormalities noted for any subject must be made available to the Site 
Monitor.
GSK Biologicals may request that the investigator perform or arrange for the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the AE or SAE. The investigator is obliged to assist. If a 
subject dies during participation in the study or during a recognised follow-up period, 
 
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GSK Biologicals will be provided with a copy of any available post-mortem findings, 
including histopathology.
8.5.
Treatment of adverse events
Treatment of any adverse event is at the sole discretion of the investigator and according 
to current good medical practice. Any medication administered for the treatment of an 
AE should be recorded in the subject’s eCRF. Refer to Section 6.1.
8.6.
Unblinding
For subjects who conclude the HPV-015 study at Visit 9 or Visit 11, but agree to remain 
blinded until the final analysis of study HPV-015, the following applies:
GSK Biologicals’ policy (incorporating ICH E2A guidance, EU Clinical Trial Directive 
and Federal Regulations) is to unblind any serious adverse event (SAE) report associated 
with the use of the investigational product, which is unexpected and 
attributable/suspected, prior to regulatory reporting. The GSK Biologicals’ Central Safety 
physician is responsible for unblinding the treatment assignment in accordance with 
specified time frames for expedited reporting of SAEs (refer to Section 8.4.1).
8.7.
Emergency unblinding
For subjects who conclude the HPV-015 study at Visit 9 or Visit 11, but agree to remain 
blinded until the final analysis of study HPV-015, the following applies:

The investigator, or other physician managing the subject, should contact GSK
Biologicals’ Central Safety Physician to discuss the need for emergency unblinding. 
Alternatively the investigator may contact the local contact who will contact the 
GSK Central Safety Physician. 

The investigator, or person designated by the investigator, should contact GSK 
Biologicals’ Central Safety physician directly or via the local safety contact (see 
below and Study Contact for Emergency Code Break in Sponsor Information page) 
to discuss the need for emergency unblinding. 

An investigator should request for unblinding of the subject’s treatment code only in 
the case of a medical emergency, or in the event of a serious medical condition, 
when knowledge of the investigational product is essential for the clinical 
management or welfare of the subject. 

The GSK Biologicals’ Central Safety Office will be allowed to access the individual 
randomisation code. The code will be broken by the GSK Biologicals’ Central Safety 
physician (see below and Study Contact for Emergency Code Break in Sponsor 
Information) only in the case of medical events that the investigator/physician in 
charge of the subject feels cannot be treated without knowing the identity of the 
study vaccine(s).
 
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For subjects concluding the HPV-015 study at the last study visit planned under protocol 
amendment 4, the HPV-062 EXT:015 study will be open label, i.e. both the investigator 
and the subject will be aware of the vaccine being administered to the subjects. 
Therefore, the information given hereunder is limited to the unblinding of SAEs to any 
third parties (e.g. any doctor other than the study investigator), in accordance with GSK 
Biologicals’ standard operating procedures.
GSK Biologicals Central Safety Physician
(Study Contact for Emergency Code Break)
Phones for 7/7 day availability:
Outside US/Canada:
 (GSK Biologicals Central Safety Physician on-call)
For US/Canada only:
(GSK Biologicals Central Safety Physician on-call)
Back-up phone contact:
Outside US/Canada:
For US/Canada only:
The investigator/delegate must instruct study subjects to carry a card (or equivalent) at all 
times during the study in order to facilitate unblinding in the event of a medical 
emergency managed by a physician other than the investigator/investigational site staff
8.8.
Subject card
Study subjects must be provided with the address and telephone number of the main 
contact for information about the trial.
Investigator/delegate should therefore provide a “subject card” to each subject. The aim 
of this card is to inform any physician having to deal with a subject in an emergency 
situation that the subject is in a clinical trial and that she can contact the trial investigator 
for more relevant information.
Subjects must be instructed to keep these cards in their possession at all times.
9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit/is available for the concluding contact 
foreseen in the protocol or who was discharged from the study, either due to treatment 
referral or due to having cleared the oncogenic HPV infection is considered to have 
completed the study.
 
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PPD
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PPD

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9.2.
Subject withdrawal
Subjects who are withdrawn because of AEs must be clearly distinguished from subjects 
who are withdrawn for other reasons. Investigators will follow subjects who are 
withdrawn as result of an SAE/AE until resolution of the event (see Section 8.4).
Withdrawals will not be replaced.
9.2.1.
Subject withdrawal from the study
From an ‘analysis’ perspective, a withdrawal’ from the study is any subject who did not 
come back for the concluding visit and who was not discharged from the study, either due 
to treatment referral or due to having cleared the oncogenic HPV infection.
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis.
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact.
Investigators will make an attempt to contact those subjects who do not return for 
scheduled visits or follow-up. 
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject herself or by the investigator, as well as which of the following possible 
reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Protocol violation (specify).

Consent withdrawal, not due to an adverse event.

Moved from the study area.

Lost to follow-up.

Death.

Other (specify).
9.2.2.
Subject withdrawal from investigational vaccine/product
Not applicable.
9.3.
Extension study
Not applicable.
 
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10.
DATA EVALUATION: CRITERIA FOR EVALUATION OF 
OBJECTIVES
10.1.
Study endpoints

Occurrence of positive oncogenic HPV DNA results in cervical samples by HPV 
DNA testing (Hybrid Capture® II test [HCII]).

Occurrence of cervical cytological abnormalities in cervical samples by ThinPrep® 
PapTest.

Occurrence of referral to colposcopy.

Occurrence of referral to treatment.
10.2.
Estimated sample size
This study is descriptive and no power evaluations will be performed. 
Approximately 1500 HPV-015 study subjects are expected to be invited to participate in 
this study.
10.3.
Study cohorts to be evaluated
The study cohort will include all subjects who attended at least one visit in the study and 
for whom data are available. No according-to-protocol cohort has been defined.
10.4.
Derived and transformed data
Not applicable.
10.5.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
10.5.1.
Sequence of analyses
Not applicable.
10.5.2.
Statistical considerations for interim analyses
No interim analysis is planned for this study.
 
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10.6.
Statistical methods
10.6.1.
Analysis of demographics/baseline characteristics
Demographic characteristics (age and gender), withdrawal status will be summarised 
using descriptive statistics:

Frequency tables will be generated for categorical variable such as race.

Mean, median, standard error will be provided for continuous data such as age. 
10.6.2.
Analysis of efficacy
Not applicable.
10.6.3.
Analysis of immunogenicity
Not applicable.
10.6.4.
Descriptive analysis of safety
For each subject and overall:

Results of oncogenic HPV DNA tests.

Results of cervical cytology tests.

Referrals to colposcopy according to management algorithm, if required.

Referrals to treatment according to local medical practice, if required.

All fatal SAEs occurring throughout the study period.

All SAEs assessed as being possibly related to study participation occurring 
throughout the study period.

All SAEs assessed as being possibly related to GSK products occurring throughout 
the study period.

Withdrawal from the study due to AEs or SAEs.
11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality and publications must be fulfilled. 
11.1.
Remote Data Entry instructions
Remote Data Entry (RDE), a validated computer application, will be used as the method 
for data collection. 
 
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In all cases, subject initials will not be collected nor transmitted to GSK. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable GSK standards and data cleaning procedures.
While completed eCRFs are reviewed by a GSK Biologicals’ Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the clinical study 
report is complete and approved by all parties.
11.2.
Monitoring by GSK Biologicals
Monitoring visits by a GSK Site Monitor are for the purpose of confirming that GSK 
Biologicals’ sponsored studies are being conducted in accordance with the ethical 
principles that have their origins in the Declaration of Helsinki and that are consistent 
with Good Clinical practice (GCP) and the applicable regulatory requirement(s) 
(verifying continuing compliance with the protocol, amendment(s), reviewing the 
investigational product accountability records, verifying that the site staff and facilities 
continue to be adequate to conduct the study). 
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform an RDE review and a Source Document 
Verification (SDV). By SDV we understand verifying RDE entries by comparing them 
with the source data that will be made available by the investigator for this purpose. 
The Source Documentation Agreement Form describes the source data for the different 
data in the RDE. This document should be completed and signed by the site monitor and 
investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the RDE will serve as the source must be identified, agreed and 
documented in the source documentation agreement form. 
For RDE, the monitor will mark completed and approved screens at each visit.
In accordance with applicable regulations, GCP, and GSK procedures, GSK monitors 
will contact the site prior to the start of the study to review with the site staff the protocol, 
study requirements, and their responsibilities to satisfy regulatory, ethical, and GSK 
requirements. When reviewing data collection procedures, the discussion will also 
include identification, agreement and documentation of data items for which the eCRF
entries will serve as the source document.
 
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GSK will monitor the study to verify that, amongst others, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any 
amendments, any other study agreements, GCP and all applicable regulatory 
requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and GSK procedures.
11.3.
Archiving of data at study sites
Following closure of the study, the investigator must maintain all site study records in a 
safe and secure location. The records must be maintained to allow easy and timely 
retrieval, when needed (e.g. audit or inspection), and, whenever feasible, to allow any 
subsequent review of data in conjunction with assessment of the facility, supporting 
systems, and staff. Where permitted by applicable laws/regulations or institutional policy, 
some or all of these records can be maintained in a validated format other than hard copy 
(e.g. microfiche, scanned, electronic for studies with an eCRF); however, caution needs 
to be exercised before such action is taken. The investigator must assure that all 
reproductions are legible and are a true and accurate copy of the original and meet 
accessibility and retrieval standards, including re-generating a hard copy, if required. 
Furthermore, the investigator must ensure there is an acceptable back-up of these 
reproductions and that an acceptable quality control process exists for making these 
reproductions.
GSK will inform the investigator/institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. However, the 
investigator/institution should seek the written approval of the sponsor before proceeding 
with the disposal of these records. The minimum retention time will meet the strictest 
standard applicable to that site for the study, as dictated by ICH GCP, any institutional 
requirements or applicable laws or regulations, or GSK standards/procedures; otherwise, 
the minimum retention period will default to 15 years. 
The investigator/institution must notify GSK of any changes in the archival 
arrangements, including, but not limited to, the following: archival at an off-site facility, 
transfer of ownership of the records in the event the investigator leaves the site. 
11.4.
Audits
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
 
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inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues.
11.5.
Ownership, confidentiality and publication
11.5.1.
Ownership
All information provided by GSK and all data and information generated by the site as 
part of the study (other than a subject’s medical records) are the sole property of GSK.
All rights, title, and interests in any inventions, know-how or other intellectual or 
industrial property rights which are conceived or reduced to practice by site staff during 
the course of or as a result of the study are the sole property of GSK, and are hereby 
assigned to GSK.
If a written contract for the conduct of the study which includes ownership provisions 
inconsistent with this statement is executed between GSK and the study site, that 
contract’s ownership provisions shall apply rather than this statement.
11.5.2.
Confidentiality
Documented evidence that a potential investigator is aware and agrees to the confidential 
nature of the information related to the study must be obtained by means of a 
confidentiality agreement.
All information provided by GSK and all data and information generated by the site as 
part of the study (other than a subject’s medical records) will be kept confidential by the 
investigator and other site staff. This information and data will not be used by the 
investigator or other site personnel for any purpose other than conducting the study. 
These restrictions do not apply to: (i) information which becomes publicly available 
through no fault of the investigator or site staff; (ii) information which it is necessary to 
disclose in confidence to an IEC or IRB solely for the evaluation of the study; (iii) 
information which it is necessary to disclose in order to provide appropriate medical care 
to a study subject; or (iv) study results which may be published as described in the next 
paragraph. If a written contract for the conduct of the study which includes 
confidentiality provisions inconsistent with this statement is executed, that contract’s 
confidentiality provisions shall apply rather than this statement.
11.5.3.
Publication
For multicentre studies, the first publication or disclosure of study results shall be a 
complete, joint multicentre publication or disclosure coordinated by GSK. Thereafter, 
any secondary publications will reference the original publication(s).
 
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Prior to submitting for publication, presentation, use for instructional purposes, or 
otherwise disclosing the study results generated by the site (collectively, a ‘Publication’), 
the investigator shall provide GSK with a copy of the proposed Publication and allow 
GSK a period to review the proposed Publication (at least twenty-one working days, or at 
least fifteen working days for abstracts/posters/presentations). Proposed Publications 
shall not include either GSK confidential information other than the study results or 
personal data on any subject, such as name or initials.
At GSK’s request, the submission or other disclosure of a proposed Publication will be 
delayed a sufficient time to allow GSK to seek patent or similar protection of any 
inventions, know-how or other intellectual or industrial property rights disclosed in the 
proposed Publication.
If a written contract for the conduct of the study, which includes publication provisions 
inconsistent with this statement is executed, that contract’s publication provisions shall 
apply rather than this statement.
12.
COUNTRY SPECIFIC REQUIREMENTS
Not applicable.
 
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13.
REFERENCES
Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin 
Virol. 2005; 32S: S16-S24.
Bosch FX, Manos MM, Munoz N et al. Prevalence of human papillomavirus in cervical 
cancer: a worldwide perspective. J Natl Cancer Inst. 1995; 87: 796-802.
Bosch FX and Munoz N. The viral etiology of cervical cancer. Virus Res. 2002; 89:183-
90.
Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16:1-17.
Clifford GM, Smith JS, Plummer M, Muñoz N and Franceschi S. Human papillomavirus 
types in invasive cervical cancer worldwide: a meta-analysis. British Journal of Cancer
(2003) 88, 6373.
Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety 
of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer 
prevention: A pooled analysis of 11 clinical trials. Hum Vaccin. 2009;5, 332-340.
Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Desy M and Rohan TE. 
Epidemiology of acquisition and clearance of cervical human papillomavirus infection in 
women from a high-risk area for cervical cancer. J Infect Dis. 1999; 180:1415-23.
Gall SA, Teixeira J, Wheeler CM, Naud P, Harper DM, Franco EL et al. Substantial 
impact on precancerous lesions and HPV infections through 5.5 years in women 
vaccinated with the HPV-16/18 L1 VLP AS04 candidate vaccine. In: American 
Association for Cancer Research Annual Meeting: Proceedings; 2007 Apr 14-18; Los
Angeles, CA. Philadelphia (PA): AACR; 2007. Abstract nr:4900.
Giannini SL, Hanon E, Moris P et al. Enhanced humoral and memory B cellular 
immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt 
combination (AS04) compared to aluminium salt only. Vaccine. 2006; 24: 5937-49. 
Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, 
Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint 
W and Dubin G. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of 
infection with human papillomavirus types 16 and 18 in young women: a randomised 
controlled trial. The Lancet. 2004;364:1757-1765.
Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins 
CM, Jenkins D, Schuind A, Costa Clemens SA & Dubin G. Sustained efficacy up to 4.5 
years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 
and 18: follow-up from a randomised control trial. The Lancet. 2006;367:1247-1255.
Harper DM, Gall S, Naud P, Quint W, Dubin G, Jenkins D and Schuind A. Sustained 
immunogenicity and high efficacy against HPV-16/18 related cervical neoplasia: Long-
term follow up through 6.4 years in women vaccinated with Cervarix™ (GSK’s HPV 
 
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16/18 AS04 candidate vaccine). Presented at: Thirty-Ninth Annual Meeting of the 
Society of Gynecologic Oncologists; 2008 Mar 10; Florida, USA: Gynecologic 
Oncology. 2008;109:158-159; Abstract nr:1.
Kirnbauer R, Booy F, Cheng N, et al. Papillomavirus L1 major capsid protein self-
assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci USA.
1992; 89: 12180-84. 
Lowy D and Howley P. Papillomaviruses. 2001; Fields Virology (D Knipe, P Howley, 
eds) 2001: 2231-64.
Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 
2000. Int J Cancer 2001a; 94: 153–56.
Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur 
J Cancer 2001b; 37(suppl 8): S4–66.
Paavonen J, Jenkins D, Bosch FX, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter 
DL, Kitchener HC, Castellsague X, De Carvalho NS, Skinner SR, Harper DM, Hedrick 
JA, Jaisamrarn U, Limson GA, Dionne M, Quint W, Spiessens B, Peeters P, Struyf F, 
Wieting SL, Lehtinen MO, Dubin G. Efficacy of a prophylactic adjuvanted bivalent L1 
virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 
in young women: an interim analysis of a phase III double-blind, randomised controlled 
trial. Lancet. 2007; 369: 2161-2170.
Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow SN, Apter D, Kitchener H, 
Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, 
Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, 
Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study 
Group, Greenacre M. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted 
vaccine against cervical infection and precancer caused by oncogenic HPV types 
(PATRICIA): final analysis of a double-blind, randomised study in young women. 
Lancet. 2009;374(a):301-14.
Pedersen C, Petaja T, Strauss G, et al. Immunization of adolescent females with human 
papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J 
Adoles Health 2007; 40: 564-571.
Schiffman M, Herrero R, DeSalle R, Hildesheim A, Wacholder S et al. The 
carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005; 
337(1): 76-84.
Schwarz TF, Spaczynski M, Schneider A, et al. Immunogenicity and tolerability of an 
HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15–55 
years. Vaccine. 2009;27 (4):581-587.
Trottier H, Mahmud S, Prado JC, Sobrinho JS, Costa MC, Rohan TE, Villa LL, Franco 
EL. Type-specific duration of human papillomavirus infection: implications for human 
papillomavirus screening and vaccination. JID. 2008: 197: 1-12. 
 
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Vernick JP, Steigman CK. The HPV DNA virus hybrid capture assay: What is it – and
where do we go from here. MLO Med. Lab. Obs. 2003;35:8-13.
Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ; ASCCP-Sponsored 
Consensus Conference. Consensus Guidelines for the management of women with 
cervical cytological abnormalities. JAMA. 2002 Apr 24; 287(16): 2120-9
Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. 
Nat Rev Cancer. 2002 (2): 342-50.
 
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Appendix A
Laboratory assays
Cytology
Cervical cytology will be performed using the ThinPrep® PapTest (Cytyc Corporation, 
Boxborough, MA, USA), by Quest Diagnostics (Teterboro, NJ, US) or another GSK 
designated laboratory. Cervical cells for ThinPrep® cytology at scheduled 12-month 
interval visits will be collected using the sampling device provided rinsed into a 
collection vial containing PreservCyt® medium (provided by GSK Biologicals or Quest 
Diagnostics).
Note that collection of cytological specimens at colposcopy will be performed according 
to local medical practice.
HPV DNA Testing by Hybrid Capture II (HCII)
After ThinPrep® cytology slides have been prepared, residual PreservCyt® specimens on 
slides read as normal or ASCUS will be tested for HPV DNA. Testing will be done by
Quest Diagnostics (Teterboro, NJ, US), or another GSK designated laboratory using the 
Hybrid Capture® II test (HCII; Digene Corp., Gaithersburg, MD, USA). Probe B will be 
used and is designed to detect infections with one of 13 oncogenic HPV types (HPV 
types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) [Vernick 2003, Digene 
Corporation 2002]. This test does not provide type-specific data.
 
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Appendix B
Amendments and Administrative Changes to the 
Protocol
GlaxoSmithKline Biologicals
Clinical Research & Development
Protocol Amendment 1
eTrack study number 
and Abbreviated Title(s)
113617 (HPV-062 EXT:015)
IND number
BB-IND 7920
EudraCT number
2009-017282-35
Amendment number:
Amendment 1
Amendment date:
Amendment 1 Final: 21 June 2010
Co-ordinating author:
 Scientific Writer
Rationale/background for changes: 

Redundant text concerning oncogenic HPV DNA test results classification was 
deleted from Section 5.4.1.

According to the protocol, histopathological reports will be performed locally and 
do not require reporting in the eCRF. This has been corrected in Section 5.4.2.

According to the protocol, colposcopy should be performed on women with two 
positive oncogenic HPV DNA tests or one cervical cytology reading ≥ASC-US 
positive for oncogenic HPV DNA or one cervical cytology reading ≥LSIL
(missing HCII test results should be managed as oncogenic HPV positive). This 
has been corrected in Section 5.5.

Oncogenic HPV testing (HCII) will only be performed on normal and ASCUS 
cytological samples. This has been corrected throughout the protocol.

It has been clarified throughout the protocol that oncogenic HPV infection status 
and cervical cytology status do not have to be recorded in the eCRF, as these data 
will automatically be transferred into the database.

The list of contributing authors has been updated.

The indication for Cervarix has been updated to be in line with the current Global 
Data Sheet.

Throughout the document, some minor corrections (including typographical and 
formatting errors) and clarifications have been performed.
 
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Amended text has been indicated in bold italics, deletions are indicated by 
strikethrough in the following sections:
Title page
Contributing authors
 Regulatory Affairs Representative
 Regulatory Affairs 
Representative
 External Laboratory Coordinator
 External Laboratory Coordinator
 Clinical Data Coordinator
 Clinical Data Coordinator
Synopsis
Indication
GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine is 
indicated in females from 10 years of age onwards for the 
prevention of pre-malignant cervical lesions and cervical 
cancer causally related to Human Papillomavirus (HPV) types 
16 and 18. Cervarix is indicated in females from 10 years of 
age onwards for the prevention of persistent infection, 
premalignant cervical lesions and cervical cancer 
(squamous-cell carcinoma and adenocarcinoma) caused by 
oncogenic Human Papillomaviruses (HPV).
Rationale for the 
study and study 
design
If very few subjects are eligible for this study at one HPV-015 
study site and if adequate gynaelogical follow-up care is 
available through the local health care system, these subjects 
may be referred to the local health care system, provided that 
ethical committee approval is obtained by the responsible 
investigator.
(Note, also amended in Section 1.2)
Study design

Study procedures:
At each visit, a gynaecological examination will be 
performed and cervical liquid-based cytology samples 
will be collected for oncogenic HPV DNA testing and
cervical cytology examination and oncogenic HPV DNA 
testing, if the cytology reading is normal or ASCUS.
The presence of oncogenic HPV infection will be 
determined by the Hybrid Capture® 2II (HC2HCII) test, 
which detects HPV DNA types 16, 18, 31, 33, 35, 39, 45, 
51, 52, 56, 58, 59 and 68 [Vernick 2003, Digene 
Corporation 2002]. Cervical cytology examination will be 
performed using the ThinPrep®Pap test.
Continued study participation as well as further 
referral/treatment will be based on the test results from 
each visit, and will be performed according to awill be 
 
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aligned with the clinical management algorithm which is 
aligned with the 2009 American Society for Colposcopy 
and Cervical Pathology (ASCCP) guidelines for use of 
HPV DNA testing as an adjunct to cytology for cervical 
cancer screening in women 30 years or older.
The following clinical management algorithm will be applied:

Subjects with normal cervical cytology and who are 
oncogenic HPV DNA negative, will end their 
participation in the study.

Subjects with normal cervical cytology, but who are 
oncogenic HPV DNA positive in one single test, will 
be asked to return at the next study visit.
This outcome will only be applicable to subjects who 
were pregnant at their concluding HPV-015 study 
visit so that no cervical sample could be collected at 
that visit.

Subjects with normal cervical cytology, but who are 
oncogenic HPV DNA positive in two subsequent 
tests, will be referred to colposcopy. The result of the 
subjects’ concluding HPV-015 study visit will be 
taken into account at Visit 1.

Subjects with a single cervical cytology reading of 
ASC-US (atypical squamous cells of undetermined 
significance) positive for oncogenic HPV DNA will 
be referred to colposcopy.

Subjects with a single cervical cytology reading of 
LSIL (low grade squamous intraepithelial lesion) 
will be referred to colposcopy, irrespective of their 
oncogenic HPV DNA test result.
Please note that a missing result for HCII will be 
managed as oncogenic HPV positive.
In case of referral for colposcopy, the post-colposcopy 
follow-up strategies are:

If no lesion is detected or the detected lesion does not 
require any treatment, subjects will be asked to return
at the next study visit. 

If a high-grade lesion that requires treatment is 
detected, the subject should be referred to treatment 
according to local medical practice. Any further 
management following local cervical therapy for 
cervical lesions will be handled according to local 
medical practice within the local health care system. 
After treatment, the subject’s participation in the 
study will end.
 
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
Study visit activities and gynaecological follow-up 
reporting

Collection of cervical liquid-based cytology samples 
at Visit 1, Visit 2, Visit 3 and Visit 4 for cervical 
cytology examination and oncogenic HPV DNA 
testing, if the cytology reading is normal or ASCUS
and recording of the results.
(Note, also amended in Section 3)
LIST OF ABBREVIATIONS
HC2HCII
Hybrid Capture 2II
(Note, this has been updated throughout the protocol)
GLOSSARY OF TERMS
Conclusion Visit of Study 
HPV-015
Subjects who participated in the HPV-015 study may 
decide to conclude their participation in the HPV-015 
study at Visit 9, Visit 11 or at the last study visit in HPV-
015 planned under protocol amendment 4.
3.
STUDY DESIGN OVERVIEW
Figure 1
Study visits and study procedures
HPV-062 study
HPV-015 study
Concluding HPV-015
visit (Visit 9 or Visit 
11 or Last Visit)
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Cervical cytology 
examination &
oncogenic HPV 
DNA test *
Study 
Conclusion **
Visit 1
12 months post 
HPV-015 V9/V11/LV
Visit 2
24 months post 
HPV-015 V9/V11/LV
Visit 3
36 months post 
HPV-015 V9/V11/LV
Visit 4
48 months post 
HPV-015 V9/V11/LV
*Subjects with two positive oncogenic HPV DNA tests or one cervical cytology reading ≥ASC-US (atypical squamous 
cells of undetermined significance) positive for oncogenic HPV DNA or one cervical cytology reading ≥LSIL (low grade 
squamous intraepithelial lesion) will be referred for colposcopy evaluation according to the clinical management 
algorithm. Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological samples.
 
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Figure 3
Clinical management algorithm
HPV-062 Visit 1, 2, 3 and 4
Cervical cytology examinationand oncogenic HPV test (HCII), if applicable$
Normal cervical cytology /
HCII negative
OR
ASC-US / HCIInegative
Normal cervical cytology / 
HCII positive
≥ASC-US / HCII positive
OR
≥LSIL 
First time: next study visit
Second time: colposcopy *
Colposcopy **
No lesion
OR
No lesion requiringtreatment
Lesion requiringtreatment
Treatmentaccording
to local practice
Study conclusion
Return to next study visit
After Visit 4
Studyconclusion
Study conclusion
HPV-062 Visit 1, 2, 3 and 4
Cervical cytology examinationand oncogenic HPV test (HCII), if applicable$
Normal cervical cytology /
HCII negative
OR
ASC-US / HCIInegative
Normal cervical cytology / 
HCII positive
≥ASC-US / HCII positive
OR
≥LSIL 
First time: next study visit
Second time: colposcopy *
Colposcopy **
No lesion
OR
No lesion requiringtreatment
Lesion requiringtreatment
Treatmentaccording
to local practice
Study conclusion
Return to next study visit
After Visit 4
Studyconclusion
Study conclusion
HPVDNA test (HC2HCII) = Hybrid Capture® 2II test detecting HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.
Specimens will be reported as “Quantity Not Sufficient” (QNS) in the case where there is an inadequate amount of cells for HC2HCII
and preferentially, a repeat sample will be collected. Missing HC2HCII test results should be managed as oncogenic HPV positive
$ = Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological samples.
5.4.1. Cytology Report Terminology
Liquid-based cytology tests and oncogenic HPV DNA tests (HCII) will be performed at 
Quest Diagnostics (Teterboro, NJ, US) or another GSK designated laboratory. Each 
cytopathological specimen will be reported according to the Bethesda 2001 Classification 
of cytological findings [Wright, 2002].
The following categories for cytology reading will be specified:

Negative for intraepithelial lesion or malignancy (negative).

Negative/HCII negative (Normal/oncogenic HPV negative)

Negative/HCII positive (Normal/oncogenic HPV positive).

Negative/HCII quantity not sufficient (Normal/QNS).

Unsatisfactory.
 
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
Atypical squamous cells of undetermined significance (ASC-US).

ASC-US/HC2II negative (ASC-US/oncogenic HPV negative)

ASC-US/HC2II positive (ASC-US/oncogenic HPV positive).

ASC-US/HC2II quantity not sufficient (ASC-US/QNS).

Atypical squamous cells cannot exclude HSIL (ASC-H).

Low-grade squamous intraepithelial lesion (LSIL).

High-grade squamous intraepithelial lesion (HSIL).

Atypical glandular cells (AGC).

Invasive malignancy.
The following categories for oncogenic HPV test (HC2) outcome will be specified:

Oncogenic HPV negative.

Oncogenic HPV positive.

Quantity Not Sufficient (QNS).
Oncogenic HPV tests (HCII) will only be performed on normal and ASCUS cytological 
samples.
The results of the cytology and HC2HCII testing will be communicated to the 
investigator (or his/her designee) by Quest Diagnostics (Teterboro, NJ, US), or another 
GSK designated laboratory. The investigator (or his/her designee) will notify the subject 
of the test result and if applicable, it is recommended that the subject should receive 
colposcopy within 30 days after cytology and HCII results have been communicated by 
Quest Diagnostics (Teterboro, NJ, US), or another GSK designated laboratory.
5.4.2. Histopathology Report Terminology
Any histopathological lesions will be biopsied or excised locally according to local 
medical practice. Histopathological reports on biopsy and excision specimens will be 
performed locally and written according to local medical practice. All histopathological 
reports will be recorded in the eCRF.
The following categories could be classified: 

Negative.

Low grade squamous intraepithelial lesion (condyloma / cervical intraepithelial 
neoplasia grade 1 (CIN1) / vaginal intraepithelial neoplasia grade 1 (VAIN 1) / 
vulval intraepithelial neoplasia grade 1 (VIN 1)).

High grade squamous intraepithelial lesion (cervical intraepithelial neoplasia grade 2 
(CIN2) / vaginal intraepithelial neoplasia grade 2 (VAIN 2) / vulval intraepithelial 
neoplasia grade 2 (VIN 2)).
 
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
High grade squamous intraepithelial lesion (cervical intraepithelial neoplasia grade 3 
(CIN3) / vaginal intraepithelial neoplasia grade 3 (VAIN 3) / vulval intraepithelial 
neoplasia grade 3 (VIN 3)).

Adenocarcinoma in-situ (AIS).
Invasive malignancy.
5.4.5. Abnormal cytology
Observation of LSIL (low grade squamous intraepithelial lesion) will result in referral 
to colposcopic evaluation, irrespective of the oncogenic HPV DNA test result.
5.5.
Colposcopic evaluation
Colposcopy will be performed according to local medical practice on women with 
abnormal cytological findings. All colposcopies will be recorded in the eCRF and every 
attempt will be made to document colposcopy performed outside the study in the specific 
section on the eCRF.
Any cervical lesions will be biopsied or excised according to local medical practice. In 
addition, the vagina and vulva may be inspected with each colposcopy and any vaginal or 
vulval lesions possibly associated with HPV (other than condylomas) may be biopsied or 
excised according to local medical practice. All tissue will be processed locally.
5.6.
Management of cervical lesions
Any further management following local cervical therapy for cervical lesions will be 
handled according to local medical practice within the local health care system. The 
treatment of cervical, vaginal or vulval lesions (or other lesions detected during the 
medical evaluation such as vaginal or vulval lesions) possibly associated with HPV is to 
be handled according to local medical practice.
5.7.
Outline of study procedures
Table 1
List of study procedures
Visit
VISIT 1
VISIT 2
VISIT 3
VISIT 4
Timing (Months post concluding HPV-015 visit 
(Visit 9, or Visit 11 or last HPV-015 study visit 
as planned in the HPV-015 protocol 
amendment 4))
Month 12
Month 24
Month 36
Month 48
Review and record oncogenic HPV infection 
status, if applicable
○**
○**
○**
○**
Review and record cervical cytology status
○**
○**
○**
○**
Record concomitant medication/vaccination, if 
applicable




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5.8.2.4.
Cervical sampling

Collect sample for cervical liquid-based cytology examination (ThinPrep® PapTest).
and oOncogenic HPV DNA (HC2HCII) testing will be performed, if applicable.
5.8.2.5.
Review and record oncogenic HPV infection status and cervical 
cytology status

Review and record oncogenic HPV infection status, if applicable.

Review and record cervical cytology status.
5.8.2.6.
Recording of referral to colposcopy and treatment (if applicable)
5.9.1.
Use of specified study materials
When materials are provided by GSK Biologicals or Quest Diagnostics, it is 
MANDATORY that all clinical samples be collected and stored exclusively using those 
materials in the appropriate manner. The investigator must ensure that his/her personnel 
and the laboratory(ies) under his/her supervision comply with this requirement. However, 
when GSK Biologicals or Quest Diagnostics does not provide material for collecting and 
storing clinical samples, then appropriate materials from the investigator’s site are to be 
used. Refer to the module of clinical trial supplies in the SPM.
5.9.4.1.
Cytology
Cervical cytology will be performed using the ThinPrep® PapTest (Cytyc Corporation, 
Boxborough, MA, USA), by Quest Diagnostics (Teterboro, NJ, US), or another GSK 
designated laboratory. Cervical cells for ThinPrep® cytology at scheduled 12-month 
interval visits will be collected using the sampling device provided and rinsed into a 
collection vial containing PreservCyt® medium (provided by sponsor GSK Biologicals 
or Quest Diagnostics).
(Note, also amended in Appendix A)
5.9.4.2.
HPV DNA Testing by Hybrid Capture 2II (HC2HCII)
After ThinPrep® cytology slides have been prepared, residual PreservCyt® specimens on 
slides for all samples read as normal or ASCUS will be tested for HPV DNA. Testing 
will be done by Quest Diagnostics (Teterboro, NJ, US), or another GSK designated 
laboratory using the Hybrid Capture® 2II test (HC2HCII; Digene Corp., Gaithersburg, 
MD, USA). Probe B will be used and is designed to detect infections with one of 13 
oncogenic HPV types (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) 
[Vernick 2003, Digene Corporation 2002]. This test does not provide type-specific data.
(Note, also amended in Appendix A)
 
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8.4.1. Prompt reporting of serious adverse events to GSK Biologicals
Back-up Study Contact for Reporting SAEs
GSK Biologicals Clinical Safety Physician& Pharmacovigilance
Fax: 
 or 
24/24 hour and 7/7 day availability
8.6.
Unblinding
For subjects who conclude the HPV-015 study at Visit 9 or Visit 11, but agree to remain 
blinded until the final analysis of study HPV-015, the following applies:
8.7.
Emergency unblinding
For subjects who conclude the HPV-015 study at Visit 9 or Visit 11, but agree to remain 
blinded until the final analysis of study HPV-015, the following applies:
GSK Biologicals Central Safety Physician
(Study Contact for Emergency Code Break)
Mobile pPhones for 7/7 day availability:
Outside US/Canada:
 (GSK Biologicals Central Safety Physician on-call)
For US/Canada only:
(Head Safety Evaluation and Risk Management 
North America GSK Biologicals Central Safety Physician on-call)
Back-up mobile phone contact: 
Outside US/Canada:
For US/Canada only:
 
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GlaxoSmithKline Biologicals
Clinical Research & Development
Protocol Administrative Change 1
eTrack study number 
and Abbreviated Title(s)
113617 (HPV-062 EXT:015)
IND number
BB-IND 7920
EudraCT number
2009-017282-35
Administrative change 
number:
Administrative change 1
Administrative change 
date:
Administrative change 1 Final: 18 August 2010
Co-ordinating author:
 Scientific Writer
Rationale/background for changes: 
Since the double-blind study HPV-015 will be extended by a maximum of three 
additional years, according to Protocol Amendment 4, dated 24 March 2010, it is 
important that central study staff involved in the studies remains blinded till the end of 
study HPV-015 for all subjects who have been participating in HPV-015 and will be 
participating in this study. Therefore, subjects enrolled in HPV-015 extension studies 
such as study HPV-062 cannot retain the HPV-015 subject number as is stated in the 
original protocol. Consequently, different identification numbers will be provided by 
an external statistician.
Amended text has been indicated in bold italics and deleted text has been indicated 
in strikethrough in the following sections:
Section 5.2.1.
Subject identification
Subjects will retain their identification numbers from study HPV-015.
A new identification number will be assigned to the subject to preserve the blind for 
HPV-015 data during this HPV-015 extension study.
 
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NOTE TO FILE 
Please use the orm be1 w to describe the Issue/incident. Ple e refer to the instructions for authors when 
completing. Tlfe use ofthis Form is optional ond may be a7apted as required. 
Alias / Abreviated Study Title (if applicable) 
E-Track Study Number (if applicable) 
Site ID (if applicable) 
HPV - 062 EXT: 015 (113617) 
113617 
All impacted site numbers 
I Upon Reconciliation/QC of Investigator Agreementlsignature pages in CARS 
I 
Initial Incident/lssue 
I (documentum) for study 113617 Portugal, it has been notice that all sites signed 
Details 
administrative change 1. 
This is true for all impacted sites as described below: 
PI -Dr. 
Site number 
 
PI - Dra 
Site number - 
 
I PI- Dra 
 Site number 
 
PI- Dra 
Site number-
 
PI- Dra 
 Site number - 
 
No signature pages were signed by Principal Investigator from the Final protocol dated, 
03 March 2010 as well Amendment 1 dated from 21 June 2010, because the studv 
I started under Administrative change 1 , from 18 August 2010. 
I 
Consequence(s) of 
Issue/incident 
Corrective Action(s) 
I 
Not all of the fdlowing sections may apply to all Note to Files. Please complete the ones that do apply. 
with justification and 
timeline(s) for 
Cause of Incident/lssue 
No signature pages were signed for the Final protocol (03 March 2010) and Amendment 
1 (21 June 2010) because the study started under Administrative change 1 (18 Aug 
2010). 
completion 
Outcome of Corrective 
Additional Information 
appended to this Note 
To File 
Please complete the signature panel below and include all stakeholders involved 
File note reporting the issue, so that signed administrative changes 1 can be indexed in 
Action(s) 
Reference documentfs) 
Note to File Templote - Version 2om of October 201 
Printed on 29/06/201 
Page 1 of 
CARS under HPV062- EXT 015 (113617) under each of the impacted sites. 
Form number FORM-GCRDCVD-OlW2-02 
GSK SOP Reference: SOP-BIOGCRDGVD-abOZVO1 
Effective 1 8  December2009 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
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113617 (HPV-062 EXT:015)
Report Final
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PPD
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NOTE TO FILE 
Farm number FORM-GCRDGVD(MO2-02 
GSK SOP Reference: SUP-BIOCCRDGVD8002~1 
Effective 1 8  Dmmk2009 
Author 
Co-Author (if 
applicable) 
Reviewed by (if 
applicable) 
Approved by (if 
applicable) 
@ 
Note to File Template - Version 2om of October 201 
Printed on 29/06/201 
Page 2 of 
Full Name and job function 
 CRA 
 
SignaJure 
Date 
29 -JUNE-2012 
29-JUNE -2012 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
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113617 (HPV-062 EXT:015)
Report Final
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14-MAR-2018
PPD
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
77
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
78
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
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113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018

 
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113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
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113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
84
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
85
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
181
14-MAR-2018
PPD
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
86
14-MAR-2018
 
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113617 (HPV-062 EXT:015)
Report Final
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Jan,i0.2e11 a:2lPM
CONFIDENTIAL
I 13617 (HPV-062 EXT;015)
Nc,3940 P,3
1 1361 7 (HPV-062 EXT:01 5)
Amendment 1
eTrnck studv number(s)
arrd Abbrevtuted Tltle(s)
IND nunrbel'
EudrnCT nurnber
Date of protocol
Date of protocol
amendment 1
Dcttlled Tttle
Invcstigotor uome
Slgnature
Date
Lelter der kllnlschen
Prtlfung'(tKP) nsme
Signnture
Drte
BB.IND 7920
2009-4fi282-35
Final: 03 March 2010
Amendment I Finall 2t June 2010
A phase IIIb, open, multi-csntre gynaecological
extension study for rhe follow-up of a suhset of HPV-
4*K t0
q
For inrerral use only
- -----.^.,Chccksunr--------!Vcr.lCreored Ort' r
a0d29259817 7 t 56s03d t 8d44 J4A 8MB 2, I 4 06/0?/201 0 I 0: I ? :5 ? -
21-JUN-2010
a9d292598777 
1 56503d 1 Ed44 s4f38b08
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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NOTE TO FILE 
Please use the orm be1 w to describe the Issue/incident. Ple e refer to the instructions for authors when 
completing. Tlfe use ofthis Form is optional ond may be a7apted as required. 
Alias / Abreviated Study Title (if applicable) 
E-Track Study Number (if applicable) 
Site ID (if applicable) 
HPV - 062 EXT: 015 (113617) 
113617 
All impacted site numbers 
I Upon Reconciliation/QC of Investigator Agreementlsignature pages in CARS 
I 
Initial Incident/lssue 
I (documentum) for study 113617 Portugal, it has been notice that all sites signed 
Details 
administrative change 1. 
This is true for all impacted sites as described below: 
PI -Dr. 
Site number 
 
PI -
Site number - 
 
I PI- 
 Site number -
 
PI- 
Site number-
 
PI- 
 Site number - 
 
No signature pages were signed by Principal Investigator from the Final protocol dated, 
03 March 2010 as well Amendment 1 dated from 21 June 2010, because the studv 
I started under Administrative change 1 , from 18 August 2010. 
I 
Consequence(s) of 
Issue/incident 
Corrective Action(s) 
I 
Not all of the fdlowing sections may apply to all Note to Files. Please complete the ones that do apply. 
with justification and 
timeline(s) for 
Cause of Incident/lssue 
No signature pages were signed for the Final protocol (03 March 2010) and Amendment 
1 (21 June 2010) because the study started under Administrative change 1 (18 Aug 
2010). 
completion 
Outcome of Corrective 
Additional Information 
appended to this Note 
To File 
Please complete the signature panel below and include all stakeholders involved 
File note reporting the issue, so that signed administrative changes 1 can be indexed in 
Action(s) 
Reference documentfs) 
Note to File Templote - Version 2om of October 201 
Printed on 29/06/201 
Page 1 of 
CARS under HPV062- EXT 015 (113617) under each of the impacted sites. 
Form number FORM-GCRDCVD-OlW2-02 
GSK SOP Reference: SOP-BIOGCRDGVD-abOZVO1 
Effective 1 8  December2009 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
88
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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PPD
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PPD
PPD
PPD
PPD
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NOTE TO FILE 
Farm number FORM-GCRDGVD(MO2-02 
GSK SOP Reference: SUP-BIOCCRDGVD8002~1 
Effective 1 8  Dmmk2009 
Author 
Co-Author (if 
applicable) 
Reviewed by (if 
applicable) 
Approved by (if 
applicable) 
@ 
Note to File Template - Version 2om of October 201 
Printed on 29/06/201 
Page 2 of 
Full Name and job function 
 CRA 
 
Sign
Date 
29 -JUNE-2012 
29-JUNE -2012 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
89
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
185
14-MAR-2018
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PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
90
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
186
14-MAR-2018
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
91
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
92
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
94
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
190
14-MAR-2018
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
95
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
191
14-MAR-2018
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
96
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
192
14-MAR-2018
PPD
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
97
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
193
14-MAR-2018
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
98
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
194
14-MAR-2018
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
99
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
195
14-MAR-2018
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
100
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
102
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
103
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
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eTrack study numberts) 
and Abbreviated Title(s) 
IND number 
EudraCT number 
Date of protocol 
Date of protocol 
amendment 1 
Date of protocol 
administrative change 1 
Detailed Title 
Investigator name 
Signature 
Date 
Leiter der klinischen 
Priifung' (LKP) name 
Signature 
Date 
CONFIDENTIAL 
11 3617 (HPV-062 EXT:OI 5) 
Administrative Change 1 
1 136 17 (HPV-062 EXT:O 15) 
BB-IND 7920 
2009-01 7282-35 
Final: 03 March 201 0 
Amendment 1 Final: 2 1 June 20 10 
Administrative Change 1 Final: 18 August 20 10 
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of HPV- 
0 15 study subjects 
Dr. Margarida Anes 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
105
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

eTrack study number(s) 
and Abbreviated Title(s) 
IND number 
EudraCT number 
Date of protocol 
Date of protocol 
amendment 1 
Date of protocol 
administrative change 1 
Detailed Title 
Investigator name 
Signature 
Date 
Leiter der klinischen 
Priifung' (LKP) name 
Signature 
Date 
CONFIDENTIAL 
1 13617 (HPV-062 EXT:015) 
Administrative Change I 
1 13617 (HPV-062 EXT:O 15) 
BB-IND 7920 
2009-0 17282-35 
Final: 03 March 201 0 
Amendment 1 Final: 2 1 June 20 10 
Administrative Change 1 Final: 18 August 20 10 
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of HPV- 
0 15 study subjects 
Dr. Elvira Bhrtolo 
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
106
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
202
14-MAR-2018
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113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
107
14-MAR-2018
 
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113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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eTrack study number(s) 
and Abbreviated Title(s) 
IND number 
EudraCT number 
Date of protocol 
Date of protocol 
amendment 1 
Date of protocol 
administrative change I 
Detailed Title 
Investigator name 
Signature 
Date 
Leiter der klinischen 
Priifung' (LKP) name 
CONFIDENTIAL 
1 1361 7 (HPV-062 EXT:015) 
Administrative Change 1 
113617 (HPV-062 EXT:015) 
BB-IND 7920 
2009-0 17282-35 
Final: 03 March 20 10 
Amendment 1 Final: 2 1 June 20 10 
Administrative Change 1 Final: 18 August 201 0 
A phase IIIb, open, multi-centre gynaecological 
extension study for the follow-up of a subset of HPV- 
0 15 study subjects 
Dr. Irene Santo 
18 AUGUST 20 10 
Signature 
Date 
 
CONFIDENTIAL
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Report Final
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24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
109
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
205
14-MAR-2018
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
110
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
206
14-MAR-2018
P
P
D
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
111
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
207
14-MAR-2018
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
112
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
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14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
114
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
115
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
211
14-MAR-2018
PPD
PPD
PPD
PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
116
14-MAR-2018
 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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14-MAR-2018
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PPD

 
CONFIDENTIAL
113617 (HPV-062 EXT:015)
Report Final
803f4ae78504c172ca582c1040b6a854a0e254e6
117
14-MAR-2018
 
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113617 (HPV-062 EXT:015)
Report Final
24b28ed5a92fffa900a7e85ab771aed0745d9d05
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