Screening HIV-Infected Women for Anal Cancer Precursors
Phase: NA
Conditions: Anal Cancer, HIV Infection, Human Papilloma Virus Infection
Sponsor: AIDS Malignancy Consortium

 
AMC #084 (Version 6.0) 21MAR2018 
 
 
1 
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AIDS MALIGNANCY CONSORTIUM 
 
 
AMC PROTOCOL #084: 
Screening HIV-Infected Women for Anal Cancer Precursors 
A Multi-Center Trial of the AIDS Malignancy Consortium (AMC) 
 
 
Sponsored by: 
National Cancer Institute 
Office of HIV and AIDS Malignancy (OHAM) 
 
NCT Registration 
Number: 
NCT01946139 
 
Regulatory Status: 
Exempt from IDE requirements [21 CFR 812.2(c)] 
 
Specimen analysis and 
support by: 
 
Gen-Probe, Inc. 
Arbor Vita Corp. 
and QIAGEN Sciences, LLC 
 
Protocol Chair: 
Elizabeth Chiao, MD 
 
Protocol Co-chair: 
Elizabeth Stier, MD 
 
Version 6.0 
21 March 2018 
NCI Version Date: 21 March 2018 

 
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AMC PROTOCOL SIGNATURE PAGE 
 
I,         , Principal Investigator at site       , agree to conduct and follow this protocol: 
Screening HIV-Infected Women for Anal Cancer Precursors (Version 6.0, 21MAR2018), as 
written according to AMC, NCI and FDA guidelines. I understand that no deviations from the 
protocol eligibility criteria or waivers for protocol deviations are permitted. 
 
 
 
_________________________________ 
_____________________ 
 
Signature 
Date (mm/dd/yyyy) 
 
 

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TABLE OF CONTENTS 
AMC PROTOCOL SIGNATURE PAGE .................................................................................. 2 
TABLE OF CONTENTS ............................................................................................................. 3 
ABBREVIATIONS ....................................................................................................................... 6 
SITES PARTICIPATING IN THE STUDY .............................................................................. 8 
PROTOCOL ROSTER ................................................................................................................ 9 
PROTOCOL SYNOPSIS ........................................................................................................... 10 
PROTOCOL SCHEMA ............................................................................................................. 11 
1.0 
BACKGROUND AND RATIONALE ........................................................................... 12 
1.1 
Background ........................................................................................................... 12 
1.2 
Rationale ............................................................................................................... 16 
1.3 
Study Design ......................................................................................................... 17 
2.0 
HYPOTHESIS AND STUDY OBJECTIVES .............................................................. 18 
2.1 
Hypotheses ............................................................................................................ 18 
2.2 
Primary Objectives................................................................................................ 18 
2.3 
Exploratory Objectives ......................................................................................... 18 
3.0 
SUBJECT SELECTION ................................................................................................. 19 
3.1 
Inclusion Criteria .................................................................................................. 19 
3.2 
Exclusion Criteria ................................................................................................. 19 
3.3 
Number of Study Participants to be Enrolled ....................................................... 19 
3.4 
Study Enrollment Procedures ............................................................................... 20 
4.0 
CLINICAL AND LABORATORY EVALUATIONS ................................................. 21 
4.1 
Schedule of Evaluations ........................................................................................ 21 
4.2 
Timing of Evaluations........................................................................................... 21 
4.3 
Special Instructions and Definitions of Evaluations ............................................. 21 
4.4 
Pathology Review ................................................................................................. 24 
4.5 
Consensus Pathology Review ............................................................................... 25 
4.6 
Follow-up for Abnormal Results .......................................................................... 25 
4.7 
Early Study Discontinuation Procedures .............................................................. 25 
5.0 
CRITERIA FOR DISCONTINUATION ...................................................................... 26 
5.1 
Early Study Discontinuation ................................................................................. 26 
6.0 
ADVERSE EVENT REPORTING ................................................................................ 27 

 
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6.1 
Expected Adverse Events Related to the Study Procedures ................................. 27 
6.2 
Classification of Adverse Events by Severity and Relationship ........................... 27 
6.3 
Routine AE Reporting........................................................................................... 28 
7.0 
STATISTICAL CONSIDERATIONS ........................................................................... 29 
7.1 
Sample Size ........................................................................................................... 29 
7.2 
Primary Statistical Analyses ................................................................................. 30 
8.0 
DATA COLLECTION AND MONITORING ............................................................. 32 
8.1 
CRF Instructions ................................................................................................... 32 
8.2 
Data Quality .......................................................................................................... 32 
8.3 
Data Monitoring .................................................................................................... 32 
8.4 
Clinical Monitoring ............................................................................................... 32 
9.0 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................ 34 
9.1 
IRB Review and Informed Consent ...................................................................... 34 
9.2 
Changes to the Protocol ........................................................................................ 34 
9.3 
Women and Minorities ......................................................................................... 34 
9.4 
Subject Confidentiality ......................................................................................... 35 
9.5 
Study Discontinuation ........................................................................................... 35 
10.0 
PUBLICATION OF RESEARCH FINDINGS ............................................................ 36 
10.1 
Study Participant Confidentiality .......................................................................... 36 
10.2 
Study Discontinuation ........................................................................................... 36 
11.0 
BIOHAZARD CONTAINMENT .................................................................................. 37 
12.0 
REFERENCES ................................................................................................................ 38 
APPENDIX I: SCHEDULE OF EVENTS ............................................................................... 42 
APPENDIX II: PERFORMANCE STATUS SCALES ........................................................... 43 
APPENDIX III: ANAL SAMPLING PROCEDURES ........................................................... 44 
APPENDIX IV: HIGH RESOLUTION ANOSCOPY (HRA) AND ANAL BIOPSIES ...... 46 
APPENDIX V: CERVICAL/VAGINAL SAMPLING PROCEDURES ............................... 47 
APPENDIX 
VI: 
PROCEDURES 
FOR 
PROCESSING 
LOCAL 
CYTOLOGY/ 
HISTOLOGY SPECIMENS AND CENTRAL PATHOLOGY REVIEW ........................... 48 
APPENDIX VII: THINPREP HPV TESTING SPECIMEN PREPARATION AND 
SHIPMENT TO THE AMC BIOREPOSITORY .................................................................... 49 
APPENDIX VIII: AMC DATA AND SAFETY MONITORING PLAN .............................. 51 
APPENDIX IX: MANAGEMENT OF ABNORMAL CYTOLOGY AND HISTOLOGY . 54 

 
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APPENDIX X: ACSR SPECIMEN PREPARATION AND SHIPPING INSTRUCTIONS 55 
APPENDIX XI: RESIDUAL CYTOLOGY SPECIMEN HANDLING AND SHIPPING .. 57 
APPENDIX XII: INFORMED CONSENT FOR OPTIONAL ACSR DONATION ........... 58 
APPENDIX XIII: BASELINE PARTICIPANT QUESTIONNAIRE ................................... 63 
APPENDIX XIV: POST-PROCEDURE TELEPHONE FOLLOW-UP QUESTIONNAIRE 
AND SCRIPT .............................................................................................................................. 79 
APPENDIX XV: FOLLOW-UP PARTICIPANT QUESTIONNAIRE ................................ 86 

 
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ABBREVIATIONS 
ACSR 
AIDS Cancer Specimen Resource 
CTEP-AERS 
CTEP Adverse Event Reporting System 
AdvantageEDCSM 
AMC Internet Data Entry System 
AE 
Adverse Event 
AIN 
Anal intraepithelial neoplasia 
AMC 
AIDS Malignancy Consortium 
ANC 
Absolute neutrophil count 
ASC-H 
Atypical squamous cells, cannot exclude HSIL 
ASC-US 
Atypical squamous cells of undetermined significance 
cART 
Combination antiretroviral therapy 
CDC 
Centers for Disease Control 
CDUS 
Clinical Data Update System 
CIN 
Cervical intraepithelial neoplasia 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety and Monitoring Board 
ELISA 
Enzyme linked immunosorbent assay 
FDA 
Food and Drug Administration 
GEE 
Generalized estimating equations 
HAART 
Highly-active antiretroviral therapy 
HIV 
Human immunodeficiency virus 
HPV 
Human papillomavirus 
HR 
High-risk 
HRA 
High resolution anoscopy 
HSIL 
High-grade squamous intraepithelial lesion(s) 

 
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IRB 
Institutional review board 
IVIG 
Intravenous immunoglobulin 
LSIL 
Low-grade squamous intraepithelial lesion(s) 
Ml 
Milliliter 
MSM 
Men who have sex with men 
NCI 
National Cancer Institute 
NILM 
Negative for intraepithelial lesion or malignancy 
OHAM 
Office of HIV and AIDS Malignancy 
OHRP 
Office for Human Research Protections 
ODMC 
Operations and Data Management Center 
PBMC 
Peripheral blood mononuclear cell 
PIO 
Protocol Information Office 
SAE  
Serious adverse event 
SCCA 
Squamous cell carcinoma of the anus 
SN 
Sensitivity 
SP 
Specificity 
STI 
Sexually transmitted infection 
TCA 
Trichloroacetic acid ablation 
VaIN 
Vaginal intraepithelial neoplasia 
VIN 
Vulvar intraepithelial neoplasia 
 
 

 
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SITES PARTICIPATING IN THE STUDY 
 
This protocol will be open to all interested AMC institutions approved by the AMC HPV Working 
Group. The approval will be based on the capacity to perform high resolution anoscopy (HRA). 

 
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PROTOCOL ROSTER 
AMC #084 
Screening HIV-Infected Women for Anal Cancer Precursors 
 
Protocol Chair: 
Statistician: 
Elizabeth Chiao, MD, MPH 
Assistant Professor of Medicine 
Baylor College of Medicine 
2002 Holcombe Blvd 
Houston, TX 77030 
Phone: (713) 794-8666 
Fax: (713) 748-7359 
Email: echiao@bcm.edu 
Jeannette Y. Lee, PhD 
AMC Statistical Center 
University of Arkansas for Medical Sciences 
4301 W. Markham, #781 
Little Rock, AR 72205-7199 
Phone: (501) 526-6712 
Fax: (501) 526-6729 
Email: jylee@uams.edu 
 
 
Protocol Co-chair: 
Operations & Data Management: 
Elizabeth Stier, MD 
Associate Professor, Obstetrics and  
Gynecology 
Boston Medical Center 
85 E. Concord St 
Boston, MA 02118 
Phone: (617) 414-5101 
Fax: (617) 414-7300 
Email: elizabeth.stier@bmc.org 
AMC Operations & Data Management Center 
The EMMES Corporation 
401 N. Washington St., Suite700 
Rockville, MD 20850 
Phone: (301) 251-1161 
Fax: (240) 238-2842 
Email: amcpm@emmes.com 
 
 
 
AMC Biorepository: 
 
Sylvia Silver, DA 
GW Biorepository 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: (202) 994-2945 
Fax: (202) 994-5056 
Email: ssilver@gwu.edu 
 
 

 
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PROTOCOL SYNOPSIS 
AMC-084: Screening HIV-Infected Women for Anal Cancer Precursors 
DESIGN: 
Prospective cohort study 
DURATION: 
Up to 2 years 
SAMPLE SIZE: 
300 
POPULATION: 
HIV-positive females 18 and older without previously 
diagnosed high-grade intraepithelial lesions (HSIL) of the anus 
or anal cancer 
REGIMEN: 
All participants will undergo anal cancer screening with anal 
cytology and several different anal HPV testing modalities 
every 6 months for up to 2 years while on study. All participants 
will undergo High Resolution Anoscopy (HRA) evaluations at 
baseline/Visit 1, Month 12/Visit 3, and Month 24/Visit 5. 
Standard screening procedures involving HRA for all abnormal 
anal cytology tests will also be performed for the interim visits. 
If diagnosed with HSIL (as defined by HSIL diagnosed on any 
anal biopsy) at any scheduled study visit, participants will 
discontinue the study early. 
PRIMARY OBJECTIVES: 
1) To determine the sensitivity and specificity of HPV testing 
using different methods of detection, including HPV 
Hybrid Capture 2 (HC2), HPV mRNA assays (APTIMA) 
and Arbor Vita OncoE6 HPV test and whether they 
improve the screening performance of routine anal 
cytology for the detection of anal HSIL when measured 
against the gold standard, biopsy-proven HSIL. 
2) To determine the prevalence and risk factors for prevalent 
HSIL in HIV-positive women. 
3) To determine incidence and risk factors associated with 
HSIL and anal HPV over 2 years among HIV positive 
women undergoing semi-annual anal evaluations. 
EXPLORATORY OBJECTIVES:  
1) To evaluate the acceptability of anal cancer screening 
among HIV-positive women. 
2) To collect data on quality of life and health care costs 
(including non-direct health care costs and time costs) for 
an economic evaluation of the cost-effectiveness of anal 
cancer screening strategies in HIV-positive women. 
 

 
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PROTOCOL SCHEMA 
 
 
 
 
 
 
 
Visit 0: Pre-Entry (Screening) 
• 
Informed consent for study participation and ACSR donation 
• 
Document HIV diagnosis, medical and medication history 
• 
Urine pregnancy test 
• 
Collect ANC and platelet count if not done for routine care ≤ 120 days prior to enrollment 
Visit 1: Enrollment (Baseline) 
• 
Baseline Questionnaire at visit 
• 
Targeted physical and anogenital exam, medical record and medication review 
• 
Collect CD4 count/percentage and HIV viral load if results not available from routine care ≤ 120 days prior 
• 
Collect 2 cervical/vaginal specimens (1 for local cytology, then 1 in ThinPrep for central HPV testing) 
• 
Collect 3 Anal Swabs (1 for local cytology, then 1 in ThinPrep for central HPV testing, and 1 swab placed 
in a lysis tube provided by ArborVita). 
• 
HRA with minimum of 2 biopsies (up to 6 directed biopsies of areas suspicious for AIN; random biopsies if 
fewer than 2 directed biopsies are taken) 
• 
Blood for ACSR donation (optional; 2 yellow top tubes if consent given; can be collected during subsequent 
visits) 
• 
Post-Procedure Questionnaire via phone call within 1-5 weeks after visit 
• 
Send cervical and anal ThinPrep specimens to AMC Biorepository within 4 weeks of collection 
Visit 2 (Month 6) AND Visit 4 (Month 18) Follow Up (-14 / +160 days) 
• 
Follow-up Questionnaire at visit 
• 
Targeted physical and anogenital exam, medical record and medication review 
• 
3 Anal Swabs (1 for local cytology, then 1 in ThinPrep for central HPV testing, and 1 swab placed in a lysis 
tube provided by ArborVita) 
• 
Send anal ThinPrep specimens to AMC Biorepository within 4 weeks of collection 
Visit 3 (Month 12) AND Visit 5 (Month 24) Follow Up (-14 days / +160 days) 
• 
Follow-up Questionnaire at visit 
• 
Targeted physical and anogenital exam, medical record and medication review 
• 
Collect CD4 count/percentage and HIV viral load if results not available from routine care ≤ 120 days prior 
for Visit 5 only 
• 
Collect 2 Cervical Swabs (1 for local cytology, then 1 in ThinPrep for central HPV testing) 
• 
Collect 3 Anal Swabs (1 for local cytology, then 1 in ThinPrep for central HPV testing, and 1 swab placed 
in a lysis tube provided by ArborVita) 
• 
HRA with minimum of 2 biopsies (up to 6 directed biopsies of areas suspicious for AIN; random biopsies if 
fewer than 2 directed biopsies are taken) 
• 
Post-procedure Questionnaire via Phone Call within 1-5 weeks after visit 
• 
Send cervical and anal ThinPrep specimens to AMC Biorepository within 4 weeks of collection 
Cytology and Histology Slide Submission Requirements 
• 
Quality Control: Submit all baseline anal histology slides collected from the first six months after enrollment 
of the first study participant at a given study site. These slides should be batch shipped to the AMC 
Biorepository as soon as possible 6 months (no more than 9 months) after enrollment of the first study 
participant at each study site. 
• 
Central Pathology Review: All anal histology slides from Visits 1-5 that were not submitted for quality 
control must be submitted for central review. All slides may be batched for submission to the AMC 
Biorepository every 6 months after the first subject’s enrollment at that site. 

 
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1.0 
BACKGROUND AND RATIONALE 
1.1 
Background 
1.1.1 Anal cancer rates among HIV-positive women in the cART era 
Anal cancer rates in HIV-positive individuals have continued to increase over the 
past decade despite the widespread use of combination antiretroviral therapy 
(cART).1-3 The highest risks appear to be among HIV-positive men who have sex 
with men (MSM);4 however, HIV-positive women are also at increased risk for 
anal cancer, with an incidence rate of approximately 10-29 per 100,000 person-
years.5,6 Chaturvedi et al 4 reported that the incidence of anal cancer among HIV-
positive women in the U.S. has increased in the post-cART era from 0 between 
1980 and 1989 to approximately 11 per 100,000 in the years between 1996 and 
2004. In addition, our research demonstrated that in the cART era, the incidence of 
squamous cell carcinoma of the anus (SCCA) increased significantly among 
women and the disease increased most rapidly among African Americans.7 Thus 
SCCA remains a growing problem for HIV-positive women, who in the United 
States are primarily African American (67%) and Latina (13%). 
1.1.2 Anal HPV, AIN, and anal carcinoma 
SCCA shares biologic similarities with cervical cancer, including detectable 
precancerous lesions and high-risk (HR) human papillomavirus (HPV) infection. 
HPV has been detected in 99% of cervical cancers and 80 to 90% of anal cancers, 
with HPV types 16 or 18 detected in about 70% of cervical and 80% of anal 
cancers.8 It is likely that the pathogenesis of anal cancer is similar to that of cervical 
cancer: that is, anal HPV infection, in conjunction with other yet to be determined 
factors, leads to the development of anal high-grade squamous intraepithelial 
lesions (HSIL), a likely precursor to anal cancer.9,10 It also has been shown that the 
rate of progression from anal dysplasia to invasive SCCA is high. Among immuno-
competent individuals, the rate of progression from anal intraepithelial neoplasia 
(AIN) to invasive SCCA has been reported as approximately 10% over a median 
time of 5 years.11,12 In a recent study of HIV-positive MSMs, 7% of 156 individuals 
who had HSIL of the anus developed invasive cancer over a median period of 8.6 
months. The authors noted that all of the individuals diagnosed with invasive cancer 
had previously refused therapy for anal dysplasia.13 Because of the high rate of 
progression from high-grade anal intraepithelial neoplasia (AIN 2,3) or HSIL14 to 
invasive SCCA, the significant morbidity and mortality associated with SCCA, and 
because SCCA shares many biologic properties with cervical cancer, several 
research and practice groups have recommended anal cancer prevention strategies 
for both HIV-positive men and women.15 
1.1.3 Anal Cancer Screening Guidelines 
There is no consensus regarding the optimal anal cancer screening strategy among 
HIV-positive individuals, particularly HIV-positive women. Prior to the 
introduction of cervical cytology screening programs, the incidence of cervical 
cancer in the U.S. was 40-50/100,000. Largely due to the success of cervical 
cytology screening, in which high-grade cervical squamous intracellular lesions 

 
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(HSIL), or cervical intraepithelial neoplasia (CIN)14 is detected and treated before 
progression to cancer occurs, the incidence of cervical cancer has declined to 8-
10/100,000. Indeed, screening with cervical cytology is considered to be one of the 
most successful cancer prevention programs.16 Because of the increased incidence 
of anal cancer, the significant morbidity and mortality associate with SCCA, and 
because of the biologic similarities between cervical and anal cancer, anal cancer 
screening programs have been proposed for both HIV-positive men and women in 
the U.S.17 
However, little data are available to determine its effectiveness. The New York 
State guidelines for primary care of HIV-positive individuals recommend screening 
HIV-positive MSM and women with a history of CIN and condyloma yearly with 
anal cytology tests.15 In contrast, the Department of Health and Human Services 
(DHHS) guidelines for the prevention and treatment of opportunistic infections 
among HIV-positive individuals states “… studies of screening and treatment 
programs for AIN 2 or 3 should not be implemented before definitive 
recommendations for anal cytology screening can be made.”18 Others have 
questioned the availability of resources needed to implement anal cancer screening 
among HIV-positive women.19 Although studies have shown anal cytology testing 
to be cost-effective among HIV-positive MSM,20,21 no such studies using female-
specific cancer screening data have been conducted among HIV-positive women, 
the target population of the current study. 
1.1.4 Anal cancer cytology test characteristics for HIV-positive women 
The reported sensitivity (SN) and specificity (SP) of anal cytology is highly 
variable, and is impacted by the type of population sampled.22,23 Several studies 
have adequately evaluated the effectiveness of anal cytology testing by comparing 
the SN and SP of the test to histology from high-resolution anoscopy (HRA) 
directed biopsy in HIV-positive men. The SNs ranged from 69% to 93%, and the 
SPs ranged from 32% to 59%.22,24 More recent studies have also shown that the SN 
and SP of anal cytology are dependent on the type of population screened, likely 
due to the variability in disease prevalence rates. Berry et al23 found that in HIV-
positive men the SN of abnormal cytology to detect high-grade anal neoplasia was 
87% and in HIV-negative MSM it was 55%. Other studies have shown that among 
HIV-positive individuals the SN and SP of anal cytology is dependent on the 
percentage of anal canal involvement.22 Anatomic differences, as well as lesion size 
and infection with multiple HR HPV types have been hypothesized to cause SN 
and SP differences. These parameters differ between HIV-positive MSM and 
women, thus, extrapolation of anal cytology test characteristics from HIV-positive 
men to HIV-positive women is likely invalid. Of note, the target sensitivity, 
specificity, positive predictive and negative predictive values lie well within the 
performance characteristics of many other well-established and widely 
recommended cancer screening modalities, including cervical cytology and 
mammography.25,26 Determining the screening test performance characteristics in 
HIV-positive women is necessary. 
1.1.5 Anal HPV and anal intraepithelial neoplasia prevalence among HIV-positive 
women 

 
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Few studies have reported estimates of anal HPV and anal cytology prevalence, and 
fewer have reported anal histology results.27,28,29 Despite the data on cervical HPV 
infection and cervical disease in HIV-positive women and data on anal HPV, 
cytologic abnormalities, and histologic abnormalities among HIV-positive men, 
there are limited data on anal HPV infection and disease among HIV-positive 
women. There have only been 4 studies describing the prevalence of HPV infection 
and anal infection among HIV-positive women.27-30 In these studies the rates of 
anal HPV varied dramatically from 16%-90% and the prevalence of anal cytologic 
abnormalities varied from 17%-39%. The variance in HPV prevalence is likely due 
to differences in the type of test performed and possibly the transport medium of 
the test. There are even less data reported regarding anal histologic diagnoses. 
Among those studies where HRA and biopsy were performed,27-28 histology results 
were only available in a small percentage of their population. Additionally, only 
one longitudinal study has been published describing incidence of anal HPV 
infection, and the cohort for this study was recruited in the pre-cART/early cART 
era.31 Therefore, further comprehensive studies in the cART era are needed to 
determine more precise estimates of factors impacting anal HPV infection, 
cytologic abnormalities, and anal histologic diagnoses. 
There are no data evaluating the screening test characteristics of U.S. Food and 
Drug Administration (FDA) -approved and experimental HR HPV testing for anal 
cancer screening among HIV-positive women. Among HIV-positive MSM, it has 
been shown that HPV testing adds little information to anal cytologic testing 
because of the very high prevalence of anal HR HPV prevalence (in most 
populations > 90%).32 However, it appears that HIV-positive women may have a 
lower rate of anal HR HPV infection; therefore, HR HPV testing may improve the 
SN and SP of anal cytology. There have been no studies evaluating HR HPV test 
characteristics among HIV-positive women, using either the FDA-approved Hybrid 
Capture 2 (HC2) test (Qiagen Corporation, Gaithersburg, MD), the APTIMA HPV 
test (GenProbe Corp, San Diego, CA), or the OncoE6™ test (Arbor Vita, Fremont, 
CA), a test that is currently in development. 
1.1.6 Hybrid Capture2 (HC2) HPV test 
In 2005 the FDA approved the use of HC2, a high-risk HPV DNA probe, as an 
adjunct to cervical cytology screening for women aged 30 years and over. HC2 
detects 13 of the HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 
68). The benefits of adding HC2 testing include: 1) having a sensitive and readily 
reproducible measure of the risk of disease and 2) having a high negative predictive 
value with a single test. The combination of the HC2 assay and cytology is also 
used in the triage of women with atypical squamous cells of undetermined 
significance (ASC-US) cervical cytology results, with an SN of 99.2% (95% 
confidence interval (CI): 97.4-100%) and an SP of 87.3% (95% CI: 84.2-90.4%) to 
detect CIN2 or worse.33  
1.1.7 APTIMA HPV Test 
The APTIMA HPV test detects messenger RNA (mRNA) for HPV proteins E6/E7 
in 14 oncogenic HPV types. Of all experimental HPV tests, the ATPIMA test has 

 
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recently received FDA approval for cervical HPV testing based on studies that have 
shown the APTIMA test to significantly improve the specificity of detecting 
CIN2+, thereby decreasing the number of “false positive” HPV tests compared to 
HC2. The test may be more predictive than the detection of HPV DNA alone 
because upregulation of mRNA from the oncogene region of the HPV genome (E6 
and E7) likely predicts which HPV infections are more likely to persist and progress 
to a high-grade lesion and cancer. The performance characteristics of APTIMA 
HPV were compared with HC2 for the detection of CIN2+ in specimens collected 
from women referred for colposcopy because of abnormal cytology. APTIMA 
HPV had an SN of 95.2% and an SP of 42.2%, compared with HC2, which had an 
SN of 99.6% and an SP of 28.4% when used without concurrent cytology.34 
1.1.8 ArborVita OncoE6™ HPV test 
The Arbor Vita OncoE6TM Cervical Test (E6 Test) is an immunochromatographic 
test applying the lateral flow format (“strip test,” conceptually similar to over-the-
counter pregnancy tests) to detect elevated levels of the HPV E6 oncoprotein from 
a cervical cytology specimen. As now demonstrated from the outcome of a clinical 
study1 performed in China, the OncoE6TM Cervical Test seems to have the potential 
to preferentially detect those women with actively transforming HPV infection 
among the much bigger group of women with clinically irrelevant HPV infection. 
The OncoE6TM Cervical Test detects E6 oncoproteins of HPV types 16 and 18 on 
two distinct test lines (“oncoprotein typing”) though monoclonal antibodies (mAb) 
specific to the targeted E6 oncoproteins, using a capture mAb / E6 / detector mAb 
sandwich principle. The E6 Test can be performed from a “dry” cervical polyester 
tipped (Dacron) swab, or from PreservCyt solution. The E6 Test can be performed 
and interpreted upon short training by anyone having none to very basic laboratory 
skills. Briefly, the cervical specimen is subjected to a simple two step lysis 
procedure, followed by a short centrifugation for lysate clearance. An aliquot of 
this lysate is allowed to run up the strip driven by capillary forces, and if E6 
oncoprotein was present in the sample, a capture mAb / E6 / detector mAb complex 
will be formed at the HPV16 and/or HPV18 test lines, respectively. The run up step 
is followed by a wash step and a development step, and then by visual inspection 
of the outcome. The time from sample collection to result is approx. 2.5 hours. The 
appearance of a control line on the strip assures proper function of the reagents, and 
a positive control (mixture of recombinant HPV 16 and 18 E6 protein) is part of the 
OncoE6TM Cervical Test kits.37  
1.1.9  Assay analytic performance 
The manufacturers of each of the three study devices will be providing support for 
the investigation in the form of assay performance at the manufacturers’ central 
laboratories.  
The devices will be used for specimen testing according to the performance 
standards for cervical evaluation outlined in the manufacturer’s device labeling and 
other published standards of performance.35,36,37,38 Each of these tests will be run 
on at least a monthly basis.47 The companies will report assay results to the AMC 
on a monthly basis for the first 6 months of the trial, which will be closely 

 
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monitored by the protocol co-chairs to determine if the sampling methods provide 
sufficient materials. The protocol will be amended if the stated sampling method 
does not consistently provide adequate material for testing. 
1.1.10 Cost-effectiveness analysis 
While clinical and epidemiologic studies are important steps in determining the 
utility of anal cytology testing among women, they provide no information on 
clinical benefits (life expectancy and quality-adjusted life expectancy), costs 
(measured in dollars), and cost-effectiveness of different anal cancer screening 
strategies for HIV-positive women. Only three papers were identified describing 
cost-effectiveness analyses of screening for anal cancer.20,39,40 Using age-specific 
HIV incidence as the only female specific data, Czoski-Murray and colleagues40 
provided the only cost-effectiveness analysis of anal cancer screening in HIV-
positive women. All other parameters were informed by data collected to populate 
the MSM screening model. A more realistic model would incorporate data from 
anal cancer screening in HIV-positive women. To address this very important 
knowledge gap, the data from this study will be used in a future economic analysis 
to assess the most cost-effective anal cancer screening approach for HIV-positive 
women. 
1.1.11 Background summary 
Determining the operating characteristics of commercially approved and soon-to-
be-approved HPV tests for anal use is necessary to inform anal cancer screening 
strategies for HIV-positive women. 
In addition, carefully constructed cost-effectiveness studies with accurate transition 
point estimates are necessary for evaluating the utility of and the best strategies for 
anal cancer screening among HIV-positive women. 
1.2 
Rationale 
The current state of anal cancer screening recommendations is similar to the state of 
cervical cancer screening recommendations in the 1960s, prior to the era of evidence-based 
medicine. Although screening for anal cancer among HIV-positive individuals has been 
endorsed by experts and promulgated by some guidelines, the available information has 
critical gaps that we will be able to address in our study: 
1) Anal cytology and HPV test characteristics: What are the screening test characteristics 
of anal cytology and commercially available or soon-to-be commercially available 
HPV tests in HIV-positive women using HRA and biopsy as the gold standard? 
2) Anal HSIL in HIV-positive women: What is the prevalence of histologically-verified 
anal HSIL? What is the incidence of anal HSIL and HPV infection? 
3) Predictors of anal HPV and HSIL in HIV-positive women: Does cervical HPV, 
behavioral, and/or immunologic characteristics, such as cART adherence and nadir 
CD4 count risk identify women at risk for anal HPV and HSIL? 
4) Poor documentation of Cost-effectiveness: What is the cost-effectiveness of anal 
cancer screening strategies in the U.S. for HIV-positive women? 

 
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By concurrently evaluating HPV tests along with anal cytology and comparing those 
results with high resolution anoscopy with directed biopsy, we will be able to ascertain the 
performance characteristics of anal cytology and HPV tests for the detection of HSIL. In 
addition, we will be able to determine the prevalence, incidence, and risk factors for HPV 
and HSIL from the longitudinal follow-up cohort study. The information gained from this 
study is crucial for the development of appropriate guidelines to screen for HSIL of the 
anus in HIV-positive women. 
1.3 
Study Design 
We propose a multi-site, 2-year longitudinal cohort study of 300 HIV-positive women who 
will be evaluated at 6-month intervals. This cohort study will be the first to provide 
important information regarding the test characteristics, epidemiology, and natural history 
of anal HPV infection and HSIL among a cohort of HIV-positive women undergoing semi-
annual anal evaluations. 

 
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2.0 
HYPOTHESIS AND STUDY OBJECTIVES 
2.1 
Hypotheses 
2.1.1 Anal HPV testing with HC2, APTIMA, or Arbor Vita OncoE6 HPV Test will 
improve the performance, including the SN and SP of anal cytology testing among 
HIV-positive women when measured against the gold standard, biopsy-proven 
HSIL. 
2.1.2 Anal HSIL and anal HPV infection are associated with risk factors including 
cervical HPV, behavioral, and immunologic characteristics, such as plasma HIV 
RNA, current CD4 and nadir CD4 counts. 
2.2 
Primary Objectives 
2.2.1 To determine the sensitivity and specificity of HPV testing using different methods 
of detection, including HPV Hybrid Capture 2 (HC2), HPV mRNA assays 
(APTIMA) and Arbor Vita OncoE6 HPV assay and whether they improve the 
screening performance of routine anal cytology for the detection of anal HSIL when 
measured against the gold standard, biopsy-proven HSIL. 
2.2.2 To determine the prevalence and risk factors for prevalent HSIL in HIV-positive 
women. 
2.2.3 To determine incidence and risk factors associated with anal HSIL and HPV over 
2 years among HIV positive women undergoing semi-annual anal evaluations. 
2.3 
Exploratory Objectives 
2.3.1 To evaluate the acceptability of anal cancer screening among HIV-positive women. 
2.3.2 To collect data on quality of life and health care costs (including non-direct health 
care costs and time costs) for an economic evaluation of the cost-effectiveness of 
anal cancer screening strategies in HIV-positive women. 

 
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3.0 
PARTICIPANT SELECTION 
3.1 
Inclusion Criteria 
3.1.1 Women age 18 and older. “Women” is defined as persons documented as female at 
birth. Younger women are not included as anal cancer is a disease of adults. 
3.1.2 HIV positive. HIV-1 infection, as documented by any federally approved, licensed 
HIV rapid test performed in conjunction with screening (or ELISA, test kit, and 
confirmed by Western blot or other approved test). Alternatively, this 
documentation may include a record demonstrating that another physician has 
documented the participant's HIV status based on either: 1) approved diagnostic 
tests, or 2) the referring physician's written record that HIV infection was 
documented, with supporting information on the participant's relevant medical 
history and/or current management of HIV infection. 
3.1.3 Karnofsky performance status ≥ 70%. 
3.1.4 Absolute neutrophil count ≥ 750 cells/mm3 within 120 days of study entry. 
3.1.5 Platelet count ≥ 75,000 cells/mm3 within 120 days of study entry. 
3.2 
Exclusion Criteria 
3.2.1 Current or history of anal or peri-anal carcinoma. 
3.2.2 History of anal HSIL cytology or histology; or anal cytology result with “ASCUS, 
cannot exclude HSIL.” 
3.2.3 Known permanent or irreversible bleeding disorder, or any illness that, in the 
opinion of the clinical investigator, would contraindicate any biopsy of the anal 
canal. 
3.2.4 For women able to conceive, evidence of pregnancy by a positive urinary 
pregnancy test within 72 hours prior to study entry. Pregnant women are excluded 
from enrollment in this study because of concerns about performing HRA during 
pregnancy. 
3.2.5 Serious medical or psychiatric illness that in the opinion of the site Investigator will 
interfere with the ability of the participant to give informed consent or adhere to the 
protocol. 
3.2.6 Ongoing use of anticoagulant therapy other than aspirin, clopidogrel, or non-
steroidal anti-inflammatory drugs (NSAIDS). 
3.2.7 Inability to provide informed consent. 
3.2.8 Treatment of anal and/or perianal HPV associated disease (i.e., condyloma or low-
grade AIN) within 4 months of study entry. 
3.3 
Number of Study Participants to be Enrolled 
3.3.1 Proposed sample size 
This study will enroll 300 participants. 

 
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3.3.2 Accrual rate 
Approximately 20 participants per month. 
3.4 
Study Enrollment Procedures 
Sites must have this protocol approved by the reviewing Institutional Review Board (IRB) 
and be registered for study participation with the AMC Operations and Data Management 
Center (ODMC) before they may enroll participants. 
3.4.1 Enrollment 
After the participant has signed informed consent, screening evaluations have been 
performed, and the participant is determined to be eligible, the participating site 
will complete the protocol-specific eligibility checklist and enroll the participant 
into AMC-084 (on-line via AdvantageEDCSM). Enrollment should occur no more 
than 1 week prior to Visit 1 (enrollment 1 day prior to or on the day of Visit 1 is 
strongly encouraged). Once the eligibility checklist is submitted, a system 
generated confirmation email will be sent to the enroller upon successful 
completion of the participant enrollment. If the on-line system is inaccessible, the 
site should notify the AMC ODMC (via email at amcpm@emmes.com or via phone 
at 301-251-1161) for further instructions. 
Participants must be enrolled into AMC-084 prior to initiating the study. 
3.4.2 Screen failure 
If a participant does not meet the eligibility criteria or refuses to take part in the 
study, a tracking sheet will be maintained locally on the number of participants 
eligible, approached, and enrolled (no PHI will be included). 

 
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4.0 
CLINICAL AND LABORATORY EVALUATIONS 
4.1 
Schedule of Evaluations 
Participants in the study will follow schedule of evaluations found in Appendix I, Schedule 
of Evaluations. 
4.2 
Timing of Evaluations 
4.2.1 Screening 
Screening evaluations must occur prior to the participant starting any study 
procedures. 
The screening and enrollment visit may be combined if the requisite laboratory 
results are available through routine clinical care. 
In addition to data being collected on participants who enroll into the study, 
demographic data and reasons for screening failures (that are available) will be 
captured in a screening log. 
4.2.2 On-study evaluations 
Evaluations must occur after participant registration. Study visits must be 
scheduled on the weeks indicated in the Schedule of Evaluations (Appendix I) from 
-14 days to +160 days for visits 2-5 for the duration of the participant's 
participation. For visit 1, all study evaluations should be completed within 50 days 
before the enrollment visit. 
4.3 
Special Instructions and Definitions of Evaluations 
All clinical and laboratory information required by this protocol is to be present in the 
source documents. All data requested by the study should be recorded in the source 
documents. All stated evaluations will be entered on the appropriate case report form 
(CRF) via the AdvantageEDCSM Internet Data Entry System unless otherwise specified. 
Quality assurance of data should follow the standards prescribed by the AMC. 
4.3.1 Medical/medication history 
Medical history 
• CDC HIV risk categories and history of AIDS defining conditions 
• History of treatment for HSIL of the cervix (CIN2,3) or cervical cancer 
• History of treatment for HSIL of the vulva (VIN2,3) or vulvar cancer 
• History of prior anal cancer screening with cytology or HRA 
• History of pelvic radiation 
• History of splenectomy 
• Presence of chronic hepatitis B or C 
• Year of HIV diagnosis 
• Nadir CD4 count (if known) 
• Allergies to any medications, including lidocaine, shellfish, or contrast agents 
• Previous history of AIDS-defining opportunistic infection 
• Listing of other past medical history 
• Topical or surgical treatment of HPV-related disease 

 
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• History of prior cervical cytologies or biopsies in the past 2 years, and most 
severe prior cervical cytology and biopsy results (if available) 
• History of prior anal cytologies or anal biopsies 
• History of systemic cytotoxic chemotherapy and/or radiation (other than pelvic 
radiation) 
A medication history must be present in source documents, including: 
• Current and past ART regimens 
• Actual or estimated start date of each agent that is part of the current cART 
therapy 
• History of any prescription medications, immune modulating herbal 
supplements, and over the counter medication taken within 14 days of study 
entry 
• History of HPV vaccination 
4.3.2 Concomitant medications/antiretroviral medication modifications 
Concomitant medications 
Use of any systemic antineoplastic or immunomodulatory treatment, systemic 
corticosteroids, investigational vaccines, interleukins, interferons, growth factors, 
or intravenous immunoglobulin (IVIG) should be documented in the CRFs. 
Any prescription medications that are not listed above that have been initiated since 
the last report should be documented in the source documents only. If the 
participant receives any dose of a HPV vaccine while on study, this must be 
documented in the source and reported in the CRFs. 
Antiretroviral medications 
Any modifications to antiretroviral medications since the last report will be entered 
on the CRFs. Modifications would include more than 14 consecutive days of missed 
antiretroviral medications. Modifications do not include change in current 
antiretroviral medication dose or formulations. 
4.3.3 Nadir CD4+ cell count 
The participant’s prior nadir CD4+ cell count (absolute value and date) should be 
documented, when possible, with a copy of the nadir CD4+ cell count report and 
entered on the CRF. If this documentation is not available, then participant 
recollection will suffice. For participants who do not know the exact nadir value 
and for whom there is no source documentation, then recall of the categorical nadir 
(e.g., < 50, < 100, < 200, 200-500, ≥ 500 cells/mm3) will suffice. If unknown, then 
the category of “unknown” will suffice. 
4.3.4 Clinical assessments 
Targeted physical exam 
This should be documented in the source documents only. A targeted physical 
examination is to include vital signs (temperature, pulse, and blood pressure) and 
assessment of Karnofsky Performance Status (KPS) (Appendix II). The rest of the 

 
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targeted exam is to be driven by any previously identified or new signs or symptoms 
including diagnoses that the participant has experienced since the last visit. 
The vulvar and perianal area will be examined for signs of HPV-related lesions. 
The presence or absence of vulvar/perianal condyloma will be recorded on the 
CRFs. Anal cytology and digital anal/rectal exam (DARE) are performed at each 
study visit. HRA with biopsy of visible disease (in the anal canal or perianus) (or 
at least 2 random sites from 2 different quadrants, if no disease is visible) will be 
performed to assess anal HPV-associated disease at visits 1, 3, and 5. Exception: If 
the participant is pregnant at visits 3 or 5, the HRA with biopsy will be deferred. 
The participant will have a cervical/vaginal speculum exam with cervical/vaginal 
cytology (for visit 1, the participant will need a specimen if not available from 
within the past 42 days) and HPV collected annually beginning with the initial 
assessment (Visit 1). 
4.3.5 Research staff administered questionnaires 
A member of the research staff will administer a questionnaire to the study 
participant at each study visit to determine her smoking status, recent sexual 
history, as well as questions to assess quality of life, acceptability of the procedure, 
ascertain costs to the participant associated with anal cancer screening. The 
estimated time to complete this questionnaire is 20 minutes. The questionnaire 
includes the EQ-5D-5L for quality of life,41 PHQ-4 for anxiety and depression,42 
the faces rating scale,43 medication adherence,44 acceptability of screening 
procedures,45 sexual behaviors,29 and personal health care cost information.46 as 
well as adapted questions on self reported HIV medication adherence46 and 
women’s experience with colposcopy.46 The baseline questionnaire (Appendix 
XIII) is administered at visit 1. The follow-up questionnaire (an abbreviated version 
of the baseline questionnaire) is administered at each subsequent visit (see 
Appendix XV). 
4.3.6 Telephone follow-up questionnaire 
The telephone follow-up questionnaire (Appendix XIV) may be conducted as a 
study visit if preferred by study staff or study participant. Each study participant 
will be contacted by the research coordinator/study nurse 1-5 weeks after each HRA 
procedure to: 
• Administer a brief questionnaire assessing perceptions/acceptability of the 
HRA; and, 
• Review the results from the HRA (cytology and biopsies). 
4.3.7 Clinical and laboratory evaluations (See Appendix I for timing of evaluations) 
• Anal cytology (See Appendix III, Anal Sampling Procedures) 
• Anal HPV studies (See Appendix III and VII, HPV Specimen Collection and 
Shipping) 
• Cervical cytology (See Appendix V, Cervical Sampling Procedures) 
• Cervical HPV studies (See Appendix V and VI) 
• Digital anal/rectal exam (DARE) 

 
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• High resolution anoscopy (HRA) with biopsy (See Appendix IV) 
• Blood collection for donation to the AIDS and Cancer Specimen Resource 
(ACSR) (two 8.5 ml yellow top tubes at ANY VISIT if the participant consents 
to donation) 
• Laboratory test results from within 120 days of enrollment include the 
following: 
o Absolute neutrophil count 
o Platelet count 
o HIV viral load: Viral load studies will be performed using an assay with 
a limit of detection of 75 copies/ml or less (visits 1 and 5 only) 
o T cells: CD4 counts and percentages will be quantified (visits 1 and 5 
only). 
• Pregnancy test for women who can conceive: Pregnancy test (urine HCG) 
will be performed (and results obtained) within 72 hours of the enrollment 
visit, at Visit 3 (12 months), and at Visit 5 (24 months) 
4.3.8 Evaluations during pregnancy 
Any participant who becomes pregnant while on study will remain on study, and 
resume normal procedures once the pregnancy resolves. While pregnant, the HRA 
procedures may be omitted due to discomfort to the participant and an absence of 
data on the effect of these procedures on a developing fetus. Anal cytology 
sampling procedures may be omitted at the preference of the participant and the 
provider, and cervical cytology procedures may still be performed if required for 
the participant’s medical care. Participants will resume all visits and procedures 
after resolution of the pregnancy. Any visits or procedures that are missed for this 
reason should be reported as missed visits and/or forms in AdvantageEDC, as 
appropriate. 
4.4 
Pathology Review 
4.4.1 Initial pathology reading: 
The specimens will first be sent to the local site’s pathology department for 
processing and pathology interpretation. Each cytology and histology specimen 
will be assigned a unique accession number in the GlobalTraceSM specimen 
tracking system for data reporting purposes and for subsequent consensus 
pathology assessments.  
Anal and cervical cytology specimens will be assigned a reading according to the 
current Bethesda System terminology: 
• Negative for intraepithelial lesion or malignancy (NILM) 
• Atypical squamous cells of undetermined significance (ASC-US) 
• Low-grade squamous intraepithelial lesion (LSIL) 
• High-grade squamous intraepithelial lesion (HSIL) 
• Atypical squamous cells, cannot exclude HSIL (ASC-H) 
• Atypical glandular cells (AGC)  
• Cancer, specify squamous cell or adenocarcinoma 

 
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Anal histology specimens will be assigned a reading as per the CAP-ASCCP LAST 
Project terminology 
• Benign/Reactive: squamous metaplasia; etc 
• LSIL (condyloma OR AIN1) 
• HSIL (AIN2, AIN2/3, or AIN3) 
• Cancer, specify squamous cell or adenocarcinoma 
Cytology and histology readings from the local cytopathology laboratories will be 
reported in the appropriate CRF in AdvantageEDCSM. 
4.5 
Consensus Pathology Review 
All anal histology slides taken during Visits 1-5 will be submitted to the AMC 
Biorepository for central pathology review. See Appendix VI for details. 
4.6 
Follow-up for Abnormal Results 
Clinical management for all study participants will be based on the local pathology 
interpretation. However, if the consensus pathology review is significantly different from 
the local pathology review, that information will be communicated to the clinical site to 
aid in patient management. 
Anal 
• If the anal cytology shows HSIL or ASC-H and no corresponding anal or perianal HSIL 
was found on HRA, then the participant should undergo another HRA in 3-6 months. 
• Further evaluation and/or treatment recommendations will be made according to HRA 
findings (See Appendix IX for recommendations regarding further evaluation and/or 
treatment). 
Cervical 
• Participants with abnormal cervical cytology should be referred for colposcopy as per 
ASCCP management guidelines (See Appendix IX). 
STUDY VISITS: (i.e., 6 month visits) participants will remain on schedule for data 
collection regardless of any interval visits for HRA, colposcopy, or treatment procedures 
(e.g., for symptomatic condyloma or HSIL of the cervix, CIN2, 3). 
Results from any abnormal follow-up and any interval treatment procedures will be 
recorded in the CRF at the subsequent scheduled study visit. 
4.7 
Early Study Discontinuation Procedures 
An Early Discontinuation form will be completed for all early study discontinuations to 
document the reason for early discontinuation. 

 
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5.0 
CRITERIA FOR DISCONTINUATION 
5.1 
Early Study Discontinuation 
• Diagnosis of histologic HSIL on any anal biopsy or cancer of the anus by either the 
local pathologists or the central pathology review at any time (including the enrollment 
visit). Only participants with benign or LSIL diagnoses on ALL anal biopsies at each 
visit will be allowed to continue in the study. Participants who have only cytologic 
HSIL diagnoses are permitted to continue on study as long as histology results do not 
show HSIL. 
• Request by participant to withdraw from the study. 
• Request of the primary care provider if s/he thinks the study is no longer in the best 
interest of the participant. 
• The participant is judged by the Investigator to be at significant risk of failing to comply 
with the provisions of the protocol as to cause harm to self or seriously interfere with 
the validity of the study results. 
• At the discretion of the AMC, IRB, Office for Human Research Protections (OHRP), 
or NCI. 
• Clinical reasons believed life-threatening by the investigator. 

 
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6.0 
ADVERSE EVENT REPORTING 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The 
following list of AEs (Section 6.1) and the characteristics of an observed AE (Section 6.2) 
will determine whether the event requires routine reporting (via AdvantageEDCSM). 
The CTEP Version 5.0 of the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) will be utilized for AE reporting. The CTEP Version 5.0 of the CTCAE is 
identified and located on the CTEP website at  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.  
All appropriate treatment areas should have access to a copy of the CTEP Version 5.0 of 
CTCAE. 
6.1 
Expected Adverse Events Related to the Study Procedures 
Anal cytology collection, HRA, and anal biopsy 
• Participants will likely experience pressure and urgency to defecate during the anal 
cytology collection and HRA. Participants may experience discomfort during the 
injection of local anesthetic (if used). There may be mild to moderate intra- and post- 
procedural pain for up to 2 weeks. Participants sometimes require pain medication post-
procedure. Rarely, this pain can be severe or last longer than 2 weeks. 
• Mild bleeding and discharge is relatively common after the procedure and may occur 
up to 2 weeks after the biopsy is taken. Rarely, there can be severe bleeding occurring 
1-2 weeks post-procedure that is severe enough to prompt an evaluation at the 
emergency room.  
• There is a slight risk (<1%) of infection or abscess post-procedure requiring antibiotics. 
6.2 
Classification of Adverse Events by Severity and Relationship 
6.2.1 Adverse Event: Any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a 
medical treatment or procedure regardless of whether it is considered related to the 
medical treatment or procedure (attribution of unrelated, unlikely, possible, 
probable, or definite). 
6.2.2 Life-threatening Adverse Event: Any AE that places the participant or participant, 
in view of the Investigator, at immediate risk of death from the reaction. 
6.2.3 Serious Adverse Event (SAE): Any AE occurring at any dose that results in any of 
the following outcomes: Death, a life-threatening AE, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/ 
incapacity, or a congenital anomaly/birth defect. 
6.2.4 Please note for hospitalization – All hospitalizations (or prolongation of existing 
hospitalization) for medical events equivalent to CTCAE Grade 3, 4, 5 must be 
reported regardless of the requirements for Phase of study, expected or unexpected, 
and attribution. For example, do not report an admission for pharmacokinetic 
sampling, but do report an admission for a myocardial infarction. 
6.2.5 Toxicity: Toxicity is a term NOT clearly defined by regulatory organizations. 
Toxicity has been described as an AE that has an attribution of possibly, probably 

 
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or definitely related to investigational treatment. To minimize confusion the NCI 
would recommend that the term toxicity NOT be utilized for AE reporting 
purposes. The CTCAE continues to use the term ‘toxicity’ because of familiarity. 
6.2.6 Unexpected Adverse Event: Any AE that is not listed in available sources including 
the package insert, the Investigator’s Brochure, or the protocol. 
6.2.7 CTEP Adverse Event Reporting System (CTEP-AERS): An electronic system for 
expedited submission of AE reports. 
6.2.8 Attribution: The determination of whether an AE is related to a medical treatment 
or procedure. Attribution categories: 
Definite – The AE is clearly related to the investigational agent. 
Probable – The AE is likely related to the investigational agent. 
Possible – The AE may be related to the investigational agent. 
Unlikely – The AE is doubtfully related to the investigational agent. 
Unrelated – The AE is clearly NOT related to the investigational agent. 
6.3 
Routine AE Reporting 
All adverse events (AEs) of Grade 3 or greater severity that are possibly, probably, or 
definitely attributed to the study procedures will be recorded on the Adverse Event Form 
in AdvantageEDCSM. Only adverse events of Grade 3 or greater severity are required for 
safety monitoring and study analysis. Adverse Event Forms will not be required for Grade 
1 and 2 AEs; these events will only require recording in source documents. Participants 
withdrawn from the study due to AEs will be followed by the Investigator until the outcome 
is determined and, when appropriate, additional written reports and documentation will be 
provided. 

 
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7.0 
STATISTICAL CONSIDERATIONS 
7.1 
Sample Size 
The primary objective of the study is to evaluate the sensitivity and specificity of the 
following methods for the detection of HSIL of the anus (as determined by consensus 
pathology): anal cytology, HPV hybrid capture 2, HPV mRNA assays (APTIMA) and 
Arbor Vita OncoE6 HPV test. Note that throughout this section, HSIL (of the anus) is 
defined as the local or consensus pathology interpretation of any anal biopsy. At the initial 
visit, all women will undergo an HRA-directed biopsy to determine if they have HSIL. 
Since HRA is considered the “gold standard,” the findings on HRA will determine whether 
a woman is classified as having HSIL or not. HSIL may be under-diagnosed due to operator 
error, thus the diagnosis of HSIL will be based on the procurement of at least 2 biopsies 
during HRA. HSIL will be thus be defined as having the diagnosis determined by either 
local pathologist or the consensus pathology on any anal biopsy at a given visit. Based on 
previous reports,41 it is anticipated that approximately 10% of women will have HSIL. The 
prevalence of HRA-proven HSIL can be estimated with a 95% confidence interval of +/- 
3.3%. 
For each of the methods of detection, the null hypothesis that the sensitivity is 50% can be 
tested against the alternative that sensitivity is at least 75% at the one-sided 0.05 
significance level with power of 0.89 with 30 HSIL participants. The HPV test results from 
all three tests-APTIMA, HC2, and HPVE6E7-are all dichotomous, i.e., reported as either 
positive or negative (or unevaluable). With 270 women who are negative for HSIL on 
HRA, the null hypothesis that specificity is 50% can be tested against the alternative 
hypothesis that specificity is at least 65% at the one-sided 0.05 significance level with 
power of 0.99. 
The novel methods of detection (HPV hybrid capture 2, HPV mRNA assays (APTIMA) 
and Arbor Vita Onco E6 HPV test) will be evaluated to determine if they improve 
sensitivity or specificity compared to routine anal cytology using McNemar’s test. With 30 
HSIL women, a 20% increase in sensitivity with 25% of participants with discordant results 
can be detected at the one-sided 0.05 significance level with 78% power. With 270 women 
negative for HSIL, a 20% increase in specificity with 25% of participants with discordant 
results can be detected at the one-sided 0.05 significance level with 99% power. Positive 
and negative predictive values will be assessed for each method of detection. 
To determine incidence of HSIL, we will use the information from the women whose initial 
HRA examination is negative for HSIL. If these women are followed for an average of 1.8 
months, we would expect 1.8 x 270 = 486 person-years of follow-up. The table below 
shows the 95% Poisson confidence intervals for two levels of the underlying incidence of 
HSIL with 486 person-years of observation: 
 
 

 
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Underlying incidence of HSIL 
per 100 person-years 
95% Poisson confidence 
interval (per 100 person-years) 
2.06 
(1.11, 3.82) 
3.09 
(1.86, 5.12) 
7.2 
Primary Statistical Analyses 
7.2.1 Primary analyses 
To estimate the sensitivity and specificity of each of the methods of detection, the 
binomial proportion and its 95% confidence interval will be used. Among 
participants who are HRA positive for HSIL, McNemar’s test will be used to 
compare routine anal cytology with each of the other methods of detection to 
determine if sensitivity in the diagnosis of HSIL is improved with the other 
methods. Similarly, among participants who are HRA negative for HSIL, 
McNemar’s test will be used to compare routine anal cytology with each of the 
other methods of HPV detection to improve specificity. Positive and negative 
predictive values will be estimated for each method of detection. 
The prevalence of HSIL will be estimated as the proportion of women who are 
HRA positive for HSIL at entry and its 95% confidence interval. Logistic regression 
analyses will be used to evaluate the association of potential risk factors (cervical 
HPV, abnormal cervical cytology, behavioral, and immunologic characteristics, 
such as plasma HIV-1 RNA, current and nadir CD4 count) with diagnosis of HSIL. 
To estimate the incidence of HSIL among women who were HRA negative for 
HSIL at study entry, the Poisson rate and its 95% confidence interval will be 
estimated from the number of HSIL cases detected divided by the cumulative years 
of follow-up across these cases. Behavioral risk factors will be assessed by research 
staff administered surveys at each study visit. Included in these risk factors is the 
risk of ongoing sexual exposure to HPV in the study population. Logistic regression 
will be used to evaluate potential risk factors for incidence of HSIL. 
To estimate the incidence of anal HPV among women who were negative for anal 
HPV at study entry, the Poisson rate and its 95% confidence interval will be 
estimated from the number of anal HPV cases detected divided by the cumulative 
years of follow-up across these cases. Logistic regression will be used to evaluate 
potential risk factors for incidence of anal HPV. 
Analysis of the results of the Arbor Vita assay will be delayed after the primary 
analysis is performed using the results of the Hybrid Capture 2 and Aptima Assays, 
if the Arbor Vita assay is optimized to yield sufficient results from anal cytology 
specimens in the future. 
7.2.2 Exploratory analyses 
We will evaluate the acceptability of anal cancer screening based on survey 
responses regarding participant satisfaction at each study visit (Appendix XIII and 
XV) and phone call surveys (Appendix XIV) administered after study visits 1, 3, 

 
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and 5. Descriptive statistics will be used to characterize participants’ acceptability 
of undergoing anal screening with cytology/HPV and HRA throughout the study to 
evaluate changes in perceptions. Generalized estimating equations (GEE) will be 
used to assess acceptability over time adjusting for intrapatient variability. 
Acceptability will be correlated with clinical and behavioral risk factors, e.g., 
history of sexual assault, depression, anxiety, medication compliance, sexual 
behaviors using GEE methods. 
A fully de-identified dataset from the study, which will include data obtained on 
quality of life, anxiety, costs, and procedures, will be made available to Professor 
Scott Cantor, MD Anderson, for an economic evaluation of cost effectiveness 
modeling of anal cancer strategies in HIV-positive women. 

 
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8.0 
DATA COLLECTION AND MONITORING 
8.1 
CRF Instructions 
Access to the internet data entry system for this study, AdvantageEDCSM, and instructions 
for recording of study data on CRFs will be provided by the AMC ODMC at 
www.amcoperations.com. Participating institutions are responsible for submitting data 
and/or data forms via AdvantageEDCSM in accordance with the AMC Data Entry Guide 
and specific form instructions, within the timelines specified by the AMC’s Standards of 
Procedure for Site Performance Measures. 
8.2 
Data Quality 
It is the responsibility of the AMC ODMC to assure the quality of data for the study (See 
Appendix VIII, AMC Data and Safety Monitoring Plan). This role extends from protocol 
development to generation of the final study database. 
8.3 
Data Monitoring 
This study will be monitored in compliance with AMC policies and by the Clinical Data 
Update System (CDUS) Version 3.0. Cumulative protocol- and participant-specific CDUS 
data will be submitted electronically to CTEP on a quarterly basis. Reports are due January 
31, April 30, July 31, and October 31. Instructions for submitting data using the CDUS can 
be found on the CTEP Web site (http://ctep.cancer.gov/reporting/cdus.html). 
The AMC ODMC is responsible for compiling and submitting CDUS data to CTEP for all 
participants and for providing the data to the Principal Investigator for review. 
8.4 
Clinical Monitoring 
The protocol chairs, AMC statistician, and AMC medical monitor will meet via conference 
call to review the protocol progress every 6 months until the final participant completes the 
last study evaluation. At all reviews, careful considerations should be given to the 
following items: 
Prevalence and incidence of HSIL. The sample size calculation was done using a 
prevalence of 10%. Substantial differences in prevalence in this study may require 
recalculation of the sample size and length of follow-up. 
Number of missing visits and number of early study discontinuations, and their effects on 
the length of intervals and loss to follow up. 
Reported adverse events. 
The protocol team members noted above will review these items and determine whether 
any modification to the study is required. If consensus about study modification or 
restarting the study is not reached among these members, then the issue will be referred to 
the AMC Executive Committee for a decision. 
The protocol chairs will monitor the quality of HRA data on a per-site basis. Only the HRA 
results for the enrollment visit (V1) will be reviewed. Specifically, the protocol chairs will 
review the proportion of participants with HSIL at each site, stratified by cytology result 
(normal vs. abnormal). It is anticipated that the proportion of participants with HSIL to be 
at least 30% in those with abnormal cytology. The median number of biopsies performed 

 
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per participant at each site will also be reviewed. 
Sites with performance evaluations that do not meet to the specified goals will contacted 
by the protocol chairs for discussion and then brought to the attention of the HPV working 
group’s HRA certification committee for re-evaluation. 

 
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9.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
9.1 
IRB Review and Informed Consent 
The principles of IRB approval and informed consent described in the Department of 
Health and Human Services (DHHS) regulations for the Protection of Human Subjects (45 
CFR Part 46) must be followed. IRB approval of the protocol and the informed consent 
form must be given in writing. 
The sponsor’s designee (AMC ODMC) must receive a copy of the letter of approval from 
the IRB, which specifically approves the protocol and informed consent, before participant 
enrollment. The IRB must also approve any significant changes to the protocol and 
documentation of this approval must be sent to the AMC ODMC. The IRB must review 
the research project at least once every 365 days during the duration of the project. 
Continuing approval of the project must also be given in writing and provided to the AMC 
ODMC. 
Records of all study review and approval documents must be kept on file by the 
Investigator and are participant to inspection during or after completion of the study. AEs 
must be reported to the IRB according to local procedures. The IRB should receive 
notification of completion of the study and final report within 3 months of study completion 
and termination. The Investigator will maintain an accurate and complete record of all 
submissions made to the IRB, including a list of all reports and documents submitted. 
Written informed consent will be obtained from the participant. The nature and significance 
of the risks associated with the study must be explained to the participant. The informed 
consent will describe the purpose of the study, the procedures to be followed, the risks and 
benefits of participation, all risks of the investigational agent(s) and/or study participation 
as listed in the model informed consent form, and all other elements of informed consent 
as required by regulation. A copy of the consent form will be given to the participant to 
keep. 
In addition, any institution(s) conducting research according to the guidelines of this 
protocol is required to adhere to local and national laws and regulations governing the 
confidentiality and disclosure of health information. 
9.2 
Changes to the Protocol 
Any change or addition to this protocol requires a written protocol amendment that must 
be approved by CTEP and the Investigator before implementation. All amendments require 
approval by the IRB of the treating institution. A copy of the IRB’s written approval must 
be sent to the ODMC.  
9.3 
Women and Minorities 
This study is being conducted by the NCI-sponsored AIDS Malignancy Clinical Trials 
Consortium (AMC). As part of their contractual obligations, each participating site within 
the AMC and the AMC as a whole is required to assure that the participation minority 
participants reflects the percentage representation of these populations in their geographic 
region and, for the AMC, the United States as a whole. As such, it is expected that the 
representation of participants on this trial will reflect the constitution of the respective 
populations. 

 
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Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
90 
+ 
0 
= 
90 
Not Hispanic or Latino 
210 
+ 
0 
= 
210 
Ethnic 
Category: 
Total 
of 
all 
subjects 
300 
+ 
0 
= 
300 
Racial Category 
 
American Indian or Alaskan Native 
0 
+ 
0 
= 
0 
Asian 
0 
+ 
0 
= 
0 
Black or African American 
210 
+ 
0 
= 
210 
Native Hawaiian or other Pacific 
Islander 
0 
+ 
0 
= 
0 
White 
90 
+ 
0 
= 
90 
Racial Category: Total of all subjects 
300 
+ 
0 
= 
300 
 
(A1 = A2) 
 
(B1 = B2) 
 
(C1 = C2) 
9.4 
Participant Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified by coded number only to maintain participant confidentiality. All records 
will be kept locked. All computer entry and networking programs will be done with coded 
numbers only. Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by the IRB, the NIH, or designee.  
9.5 
Study Discontinuation 
The study may be discontinued at any time by the IRB, the NIH, or other government 
agencies as part of their duties to ensure that research participants are protected. 

 
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10.0 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by AMC policies. Any presentation, 
abstract, or manuscript will be made available for review prior to submission.  
10.1 
Study Participant Confidentiality 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number only and de-identified from the participant. 
Clinical information will not be released without written permission of the participant, 
except as necessary for monitoring by the FDA, OHRP, the AMC, or the NCI. 
10.2 
Study Discontinuation 
This study may be discontinued at any time by the NCI, the AMC, the OHRP, or the FDA. 

 
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11.0 
BIOHAZARD CONTAINMENT 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood and shipping and 
handling of all specimens for this study, as currently recommended by the Centers for 
Disease Control and Prevention and the National Institutes of Health. 
All dangerous goods materials, including diagnostic specimens and infectious substances, 
must be transported according to the instructions detailed in the International Air Transport 
Association (IATA) Dangerous Goods Regulations. 

 
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12.0 
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31. Durante AJ, Williams AB, Da Costa M, Darragh TM, Khoshnood K, Palefsky JM. Incidence 
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PE. An Evaluation of Novel, Lower-Cost Molecular Screening Tests for Human 
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A, Castle PE, Cheng S. Direct human papillomavirus E6 whole-cell enzyme-linked 
immunosorbent assay for objective measurement of E6 oncoproteins in cytology samples. 
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39. Goldie SJ, Kuntz KM, Weinstein MC, Freedberg KA, Palefsky JM. Cost-effectiveness of 
screening for anal squamous intraepithelial lesions and anal cancer in human 
immunodeficiency virus-negative homosexual and bisexual men. Am J Med. Jun 1 
2000;108(8):634-641. 
40. Czoski-Murray C, Karnon J, Jones R, Smith K, Kinghorn G. Cost-effectiveness of screening 
high-risk HIV-positive men who have sex with men (MSM) and HIV-positive women for 
anal cancer. Health Technol Assess. Nov 2010;14(53):iii-iv, ix-x, 1-101. 
41. Pickard AS, De Leon MC, Kohlmann T, Cella D, Rosenbloom S. Psychometric comparison of 
the standard EQ-5D to a 5 level version in cancer patients. Med Care. Mar 2007;45(3):259-
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42. Kroenke K, Spitzer RL, Williams JB, Lowe B. An ultra-brief screening scale for anxiety and 
depression: the PHQ-4. Psychosomatics. Nov-Dec 2009;50(6):613-621. 
43. Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-
Revised: toward a common metric in pediatric pain measurement. Pain. Aug 
2001;93(2):173-183. 
44. Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral 

 
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medications among participants in HIV clinical trials: the AACTG adherence instruments. 
Patient Care Committee & Adherence Working Group of the Outcomes Committee of the 
Adult AIDS Clinical Trials Group (AACTG). AIDS Care. Jun 2000;12(3):255-266. 
45. Vajdic CM, Anderson JS, Hillman RJ, Medley G, Grulich AE. Blind sampling is superior to 
anoscope guided sampling for screening for anal intraepithelial neoplasia. Sex Transm 
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46. Cantor SB, Levy LB, Cardenas-Turanzas M, et al. Collecting direct non-health care and time 
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47. ArborVita, Inc. representative. Telephone communication. Feb-Mar 2014. 

 
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APPENDIX I: SCHEDULE OF EVENTS 
Evaluation 
Screening 
 
Enrollment¥ 
(Visit 1) 
(Baseline) 
Post-Procedure 
Call (2-5 weeks 
after V 1, 3, 5) 
Visit 2* 
Month 6 
Visit 3* 
Month 12 
Visit 4* 
Month 18 
Visit 5* 
Month 24 
Informed consent 
X 
 
 
 
 
 
 
Documentation of HIV 
X 
 
 
 
 
 
 
Medical history, medication history, ANC, platelets 
X1 
 
 
 
 
 
 
Medical record review, HIV viral load, CD4 count2 
 
X 
 
 
 
 
X 
Pregnancy test (urine) 
X 
X3 
 
 
X 
 
X 
Baseline questionnaire  
 
X 
 
 
 
 
 
Post procedure questionnaire via phone call 
 
 
X 
 
 
 
 
Follow-up questionnaire 
 
 
 
X 
X 
X 
X 
Targeted physical and anogenital exam 
 
X 
 
X 
X 
X 
X 
Anal cytology4 
 
X 
 
X 
X 
X 
X 
Anal swab for HPV (1 in ThinPrep) 
 
X 
 
X 
X 
X 
X 
Anal swab in lysis tube for Arbor Vita 
 
X 
 
X 
X 
X 
X 
Cervical cytology5 
 
X 
 
 
X 
 
X 
Cervical swab for HPV (1 in ThinPrep) 
 
X 
 
 
X 
 
X 
HRA with biopsy of lesions6 
 
X 
 
 
X 
 
X 
Anal cytology slides7 
 
X 
 
X 
X 
X 
X 
Anal biopsy slides7 
 
X 
 
 
X 
 
X 
ACSR blood specimen (participant consent) 
 
X 
 
 
 
 
 
* Visits 2-5 (and associated specimens) may occur within 14 days prior to the target visit date and up to 160 days after the target visit date. 
¥ All Study Evaluations for Enrollment visit must be completed within 50 days before the enrollment visit. 
1. Only collect ANC and platelets if results are not available from routine clinical care within 120 days before enrollment. 
2. Only collect HIV viral load and CD4 counts/percentages if results are not available from routine clinical care within 120 days before Visit 1 and Visit 5. 
3. Pregnancy test will not be required at Visit 1 if the pregnancy test for Screening/eligibility review was performed less than 72 hours prior to study entry. 
4. Local anal cytology specimens may be collected in liquid medium as per standard of care of study site (either ThinPrep or Surepath). 
5. For the enrollment visit local cervical cytology specimens may be collected up to 42 days before the enrollment visit date. 
6. Perform HRA-directed biopsies up to 6 of the most abnormal appearing areas. Each study participant will have at least two biopsies at HRAs (visits 1, 3, 5). 
If fewer than two directed biopsies are taken from two different quadrants, then random biopsy/biopsies will be done such that there will be at least two 
biopsies from at least two different quadrants. These biopsies can be from the anal canal or perianus. 
7. All baseline anal cytology slides for the first 6 months after a site is activated will be submitted for an evaluation of quality control. All anal histology slides 
taken during Visits 1-5 will be submitted to the AMC Biorepository for central pathology review. Slides will be submitted as per Appendix VI for details. 

 
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APPENDIX II: PERFORMANCE STATUS SCALES 
 
Karnofsky Performance Scale 
 
 
ECOG Performance Status Scale 
Percent 
Description 
Grade 
Description 
100 
Normal, no complaints, no 
evidence of disease. 
0 
Normal activity. Fully active, able 
to carry on all pre-disease 
performance without restriction. 
90 
Able to carry on normal activity; 
minor signs or symptoms of 
disease. 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
1 
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able to 
carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
70 
Cares for self, unable to carry on 
normal activity or to do active 
work. 
60 
Requires occasional assistance, 
but is able to care for most of 
his/her needs. 
2 
In bed <50% of the time. 
Ambulatory and capable of all self-
care, but unable to carry out any 
work activities. Up and about more 
than 50% of waking hours. 
50 
Requires considerable assistance 
and frequent medical care. 
40 
Disabled, requires special care 
and assistance. 
3 
In bed >50% of the time. Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
20 
Very sick, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely 
disabled. Cannot carry on any self-
care. Totally confined to bed or 
chair. 
10 
Moribund, fatal processes 
progressing rapidly. 
0 
Dead. 
5 
Dead. 

 
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APPENDIX III: ANAL SAMPLING PROCEDURES 
All anal cytology specimens will be examined at the local institution. 
The participant should undress from the waist down, and either bend over the exam table or lay on 
their side in the fetal position. The examiner should use one hand to spread the buttocks and expose 
the anal verge. 
Procedure for obtaining an anal swab specimen 
A Dacron swab moistened in tap water will then be inserted as far as is comfortable into the anus, 
a minimum of 1-2 inches. If there is difficulty inserting the swab, the participant should also retract 
their buttocks and the swab reoriented in the canal. With pressure on the distal end of the swab 
rotate it firmly in a circular fashion for approximately 20 seconds and slowly remove from the 
canal. Do not retract the buttocks when the swab is close to the verge to ensure that it is sampled 
as well. Immediately immerse the swab in a liquid-cytology vial agitating vigorously over 20 to 
30 seconds to disperse the cells.  
The order of anal specimen collection will be determined at the time of registration and will remain 
constant for a given participant for every study visit. 
The three anal swab specimens will be collected from each study participant in the order as 
designated at the time of enrollment. The sequence of collection for these three swabs will be 
randomly assigned by the data entry system, AdvantageEDC, at the time of enrollment. The 
site should print the collection order for the specimens in the enrollment confirmation email 
message and save it to the study file for future reference. 
Anal swab specimens for a given study participant will always be collected in the same 
sequence at every visit. For example, participant 1 may be assigned to have specimens collected 
in the order “local,” “thinprep”, and “lysis” at all visits, whereas participant 2 may be designated 
the order “thinprep,” “lysis,” and “local” at all visits, etc. The three swabs collected are: 
• Dacron Swab “local” [Identified as “Dacron Swab (local cytology)” in the swab sequence 
assignment at enrollment]. This swab will be placed in the cytology medium required for local 
processing for anal cytology. 
• Dacron Swab “thinprep” [Identified as “Dacron Swab (ThinPrep HPV)”]. This swab will be 
placed in a 20 mL ThinPrep (PreservCyt) media vial (for research anal HPV analyses) and 
stored in a refrigerator (2-8° C) as soon as possible after collection. 
• Puritan Medical Products Dacron Swab “lysis” [Identified as “Swab for Arbor Vita ("lysis" 
tube)”]. This swab will be placed in a tube provided by Arbor Vita (a.k.a., “lysis” tube) 
immediately after collection. The swab stem will be broken to deposit the entire swab head so 
that the cap will fit on the tube. Instructions on isolating the swab head in the lysis tube can be 
found on the AMC AIDS Malignancy Consortium website at www.amcoperations.com. Anal 
swabs placed in the Arbor Vita-supplied tubes should be frozen immediately at -80° C. The 
sites may batch ship these specimens EVERY 3 months. 
Note: While the anal specimen collected for Arbor Vita will be stored “dry,” the swab may be pre-
moistened with tap water before the sampling procedure for patient comfort. 
Sites are strongly encouraged to implement local processes to ensure that the assigned anal 

 
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cytology swab specimen collection sequence is maintained during the study. Sites should label 
swab collection tubes with the assigned collection sequence using a marker before sampling. The 
actual collection sequence must be documented in the source for each anal sampling procedure. A 
sample source document for this purpose is provided on the AMC AIDS Malignancy Consortium 
website at www.amcoperations.com.Sites will be required to report the actual sequence of 
swab collection in the data entry system. 
The Puritan swab will be provided by the AMC, and the “lysis” tube for the Arbor Vita swab will 
be provided by Arbor Vita. The ODMC will place all orders for the Puritan swabs and collection 
tubes for the dry swab specimen on the site’s behalf. All requests for supplies may be placed with 
the AMC ODMC via email (amcpm@emmes.com) or fax (240-238-2842). This request may be 
made using the attached AMC-084 Cytology Supplies Request Form. The Cytology Supplies 
Request Form can be found on the AMC AIDS Malignancy Consortium website at 
www.amcoperations.com. 
Arbor Vita: Use the Puritan™ Polyester-Tipped Applicator to obtain the anal specimen and then 
place the swab in a 1.5ml eppendorf tube (lysis tube) and store the lysis tubes at -80oC. Site will 
then batch ship the lysis tubes on dry ice to the AMC Biorepository every 3 months. See the AMC-
084 MOP for shipping instructions. 

 
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APPENDIX IV: HIGH RESOLUTION ANOSCOPY (HRA) AND ANAL BIOPSIES 
Procedure for performing HRA 
High resolution anoscopy should only be done after the specimens for anal cytology and HPV 
testing are collected. The patient will already be positioned for anal evaluation. A mixture of a 
topical anesthetic (e.g., 2% lidocaine jelly or EMLA ointment) and water-soluble lubricating jelly 
should be used as a lubricant. A digital anal/rectal exam should be performed noting any masses 
or areas of induration. The procedure for HRA is as follows: 
1) Insert the plastic disposable anoscope, remove obturator, and place a cotton swab wrapped in 
gauze soaked in 3-5% acetic acid into anus. 
2) Remove the anoscope over the swab and leave in place for 1 to 2 minutes. 
3) Remove the swab and re-insert the anoscope. Carefully examine the anal canal with a 
colposcope. 
4) Re-apply acetic acid as necessary to ensure adequate detection of lesions. 
5) If acetowhitening is noted, note vascular characteristics, if present. 
6) Lugol’s solution (iodine) may be used to aid identification of possible AIN near the 
squamocolumnar junction. 
7) Biopsy up to six of the most abnormal appearing areas (directed biopsies) clinically suspicious 
for AIN. Local anesthetic (e.g., 1% lidocaine with or without epinephrine or .5% bupivicaine) 
may be used at the provider’s discretion prior to biopsy. 
8) Each study participant will have at least two biopsies. If fewer than two directed biopsies are 
taken from two different quadrants, then random biopsy/biopsies will be done such that there 
will be at least two biopsies from at least two different quadrants. 
9) Attain hemostasis prior to removal of the anoscope (with pressure, Monsel’s solution, or silver 
nitrate). 
10) An external genital exam should be performed to note the presence of condyloma and other 
abnormalities. 
11) Apply acetic acid to perianal area and examine carefully with colposcope. 
12) Biopsy any external (perianal) areas clinically suspicious for AIN, using a local anesthetic 
(e.g., 1% lidocaine with or without epinephrine or .5% bupivicaine) prior to biopsy. 
13) Participants with signs or symptoms consistent proctitis or sexually transmitted infections 
other than HPV should be referred for appropriate diagnosis and treatment. 

 
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APPENDIX V: CERVICAL/VAGINAL SAMPLING PROCEDURES 
Procedure for obtaining cervical/vaginal cytology samples 
The participant should undress from the waist down, and lay on her back on the exam table. The 
examiner should follow standard pelvic exam procedures. Collection for two cervical* specimens 
will be collected. The cervical cytology specimen (using the “broom”, cytobrush, and/or spatula) 
will be collected first, and will be placed in the standard liquid-based cytology media at each local 
institution (e.g., ThinPrep or SurePath). The second specimen will be collected by “broom,” 
cytobrush, and/or spatula and dispersed in a 20 ml vial of ThinPrep (PreservCyte) to be used for 
all three HPV analyses.  
See Appendix VI for local processing of the first sample for cytology. 
See Appendix VII for processing and shipping of the second sample collected for HPV 
analyses. 
*If the participant has had a hysterectomy, then the specimens should be collected from the 
vaginal apex instead of the cervix.  

 
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APPENDIX VI: PROCEDURES FOR PROCESSING LOCAL CYTOLOGY/ 
HISTOLOGY SPECIMENS AND CENTRAL PATHOLOGY REVIEW 
Local cytology/pathology specimen processing 
1) Local cytology reading: Run the liquid cytology sample (ThinPrep or Surepath) as is, per 
protocol at the local institution. The reading from the cytopathology lab will be submitted in 
the appropriate eCRF in AdvantageEDC. The study investigators will have access to the 
cytopathology reading via the AMC Operations web site (secure access). 
2) Residual specimens: If the participant consented to donate residual study specimens to the 
ACSR for future testing, the residual liquid cytology medium after performing the local anal 
and cervical cytology readings will be sent to AMC Biorepository within 4 weeks of specimen 
collection (see Appendix XI for labeling and shipping requirements). 
3) Histology: Process as per protocol at the local institution. The reading from the pathology lab 
will be submitted in the appropriate eCRF in AdvantageEDC. The study investigators will have 
access to the cytopathology reading via the AMC Operations web site (secure access). 
Suggested p16 immunohistochemical (IHC) staining for local pathologists 
1) To differentiate between the H&E morphologic diagnosis of precancer (–IN 2 or –IN 3) and a 
mimic of precancer (e.g., processes known to be unrelated to neoplastic risk such as immature 
squamous metaplasia, atrophy, reparative epithelial changes, tangential cutting). Strong and 
diffuse block-positive p16 results support a categorization of precancerous disease. 
2) To clarify a diagnosis of –IN2 in an H&E morphologic interpretation of –IN 2 (under the old 
terminology), which is a biologically equivocal lesion falling between the morphologic 
changes of HPV infection (low-grade lesion) and precancer. Strong and diffuse block-positive 
p16 results support a categorization of precancer. Negative or non–block-positive staining 
strongly favors an interpretation of low-grade disease or a non–HPV-associated pathology 
Central pathology review 
• Please review the MOP for central pathology slide shipping instructions and central pathology 
review.  
For quality control, each site will submit all baseline histology study slides used for screening 
evaluation, including any stained slides, collected from the first six months after enrollment of 
the first study participant at a given study site. These slides should be batch shipped to the 
AMC Biorepository as soon as possible up to 9 months after enrollment of the first study 
participant at each study site. All anal histology slides taken during Visits 1-5 will also be 
submitted to the AMC Biorepository for central pathology review. The AMC Biorepository 
will distribute all slides except those originating from UCSF to Dr. Teresa Darragh at UCSF 
for review, and will ship all slides originating from UCSF to Baylor College of Medicine for 
review. Central review from the participating pathologists will be returned to study sites within 
6-8 weeks of receipt. 

 
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APPENDIX VII: THINPREP HPV TESTING SPECIMEN PREPARATION AND 
SHIPMENT TO THE AMC BIOREPOSITORY 
All anal and cervical specimens that are collected in ThinPrep for HPV testing on this 
protocol must be submitted to the AMC Biorepository within 4 weeks of collection. Prior to 
shipment, store all anal and cervical ThinPrep specimens for HPV testing at 2-8°C. Once received, 
the AMC Biorepository will aliquot and ship specimens for analysis at each of the three companies 
performing HPV testing for this protocol. Aliquot preparation requirements and the shipment 
schedule for distributing samples to each of the three companies are outlined in the AMC-084 
Biorepository Manual of Procedures.  
The “dry” Dacron swab in the lysis tube must be submitted to the AMC Biorepository within 
3 months of collection. Prior to shipment, these anal swabs need to be stored at -80o C. The 
AMC Biorepository will then ship the specimens to Arbor Vita. 
Cervical Specimens for HPV Analysis 
The protocol requires collection of cervical specimens for HPV analysis for each participant at 3 
study visits: Baseline (0), 12, and 24 months. The ThinPrep media vial for cervical HPV analysis 
should be placed in refrigeration (2-8° C) as soon as possible after collection. 
NOTE: Anal and Cervical ThinPrep Specimens MUST BE SHIPPED on ice packs. The anal swab 
in the lysis tube must be shipped on DRY ICE. Specimens should be shipped on MONDAYS (OR 
TUESDAY IF MONDAY IS A HOLIDAY) using PRIORITY OVERNIGHT service.  
Ship the Specimens to:  
Dr. Sylvia Silver 
GW Biorepository 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: (202) 994-2945 
Fax: (202) 994-5056 
ThinPrep Sample Labeling 
Samples must be labeled with the bar-coded labels provided. Each sample should be labeled with 
the following information: 
Participant ID: “084-XXX-XXX” 
Specimen Type: "Cytology Medium” 
Specimen Purpose: “Cervical HPV” or “Anal HPV” 
Date of Sample Collection: MM/DD/YYYY 
Shipping Instructions 
To ship anal and cervical ThinPrep specimens, use a diagnostic shipper approved for a volume of 
at least 30 cc. The use of the SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. 
These shippers may be ordered at the SAF-T-PAK website www.saftpak.com. The following 
instructions below are for use with the recommended STP-210 shipper. If using another federally 

 
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approved diagnostic shipper, please follow instructions provided for that specific shipper. Use 
FedEx account #: 352207845. 
Record of Specimens 
This study will track specimens via GlobalTraceSM, a component of the AMC AdvantageEDCSM 
system. The GlobalTrace shipment manifest must accompany all specimens. 

 
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APPENDIX VIII: AMC DATA AND SAFETY MONITORING PLAN 
(Version 6.0  March 17, 2017) 
 
Monitoring the Progress of Trials and the Safety of Participants 
All AMC protocols that collect safety data follow the National Cancer Institute (NCI), Cancer 
Therapy Evaluation Program (CTEP) Guidelines: Adverse Event Reporting Requirements 
(http://ctep.cancer.gov/guidelines/index.html). All adverse events that meet the NCI’s expedited 
reporting requirements are reported to the Investigational Drug Branch (IDB) of the NCI via the 
CTEP Adverse Event Reporting System (CTEP-AERS) web application. All expedited adverse 
event reports are also required to be submitted to the local Institutional Review Board (IRB) of the 
reporting institution. If NCI holds the IND or no IND is required for a study, the AMC site reports 
serious adverse events directly to the AMC Operations and Data Management Center (ODMC) via 
CTEP-AERS; expedited reporting via AdvantageEDC/Advantage eClinical may be permitted for 
select commercial agent studies per protocol requirements. In some instances, the AMC sites may 
report serious adverse events directly to a commercial sponsor holding the IND, who will then 
report the event to the AMC ODMC. Most AMC protocols require sites to report all serious 
adverse events via CTEP-AERS and the AMC ODMC to forward a copy of the report to the 
sponsor. The AMC ODMC also distributes all IND safety reports to all investigators upon receipt, 
and makes these reports available on the password-protected section of the AMC Operations web 
site. Unless an AMC protocol specifies an alternate plan for the review and submission of serious 
adverse events, all serious adverse events received by the AMC ODMC will be reviewed by the 
AMC Medical Monitor at the AMC ODMC. For protocols for which the IDB does not have an 
assigned drug monitor to review serious adverse event reports, in the event of disagreement 
between the reporting physician and the AMC Medical Monitor regarding the attribution of the 
event to the investigational agent(s) (i.e., determination of whether the relationship is unrelated, 
unlikely, possible, probable, or definite), the AMC Medical Monitor will provide the final 
determination of the relationship. 
The AMC ODMC provides listings of all reported adverse events and serious adverse events to 
the Protocol Chair and Co-chair(s) for review on a regular basis. The AMC ODMC compiles these 
events in a tabular format and posts them on the password-protected section of the AMC web site 
where these reports are updated nightly. The AMC web site is accessible to all AMC investigators, 
co-investigators, and their staff. Email notification that this information is available on the web 
site will be sent to all site PIs. It is the responsibility of each site to provide this information to 
their respective IRBs, if required by their IRB. For blinded studies, the serious adverse events are 
reviewed and tabulated without treatment assignment. The AMC Medical Monitor will review 
listings of all reported adverse events on a quarterly basis for safety concerns. 
Accrual summaries for each AMC trial are updated nightly on the password-protected section of 
the AMC web site. The progress of each AMC trial is reviewed regularly by the Protocol Chair 
and also by the appropriate disease-oriented Working Group during scheduled conference calls. 
For phase I dose escalation trials, dose escalation (or dose de-escalation) is based on the rules in 
the protocol and the Protocol Chair, AMC Medical Monitor, and Group Statistician determine 
whether these criteria have been met. For phase II trials, stopping the trial for toxicity or efficacy, 
or suspending enrollment pending observation of responses in a multi-stage phase II trial, is based 
on meeting criteria stated in the protocol, and the Protocol Chair, AMC Medical Monitor, and 

 
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Group Statistician determine whether these criteria have been met. 
For phase III trials and other select studies requiring additional oversight, the AMC has formed an 
independent Data and Safety Monitoring Board (DSMB). Voting members of the DSMB are 
physicians, a statistician, and a patient advocate. All voting members are from outside the AMC. 
Nonvoting members are the AMC Group Statistician, the protocol statistician, an AMC Operations 
Center staff member, two representatives (normally a clinician or statistician) from the Office of 
HIV AIDS Malignancy (OHAM) or from the Cancer Therapy Evaluation Program, Division of 
Cancer Treatment and Diagnosis, of the National Cancer Institute (NCI). The DSMB reviews 
AMC phase III studies in accordance with the National Cancer Institute’s Policy for Data and 
Safety Monitoring. Confidential reports of all phase III trials are prepared by the AMC Group 
Statistician with support from the AMC ODMC. A written report containing the current status of 
each trial monitored, and when appropriate, any toxicity and outcome data, are sent to DSMB 
members by the AMC ODMC within the timelines specified by the DSMB Charter. This report 
addresses specific toxicity concerns as well as concerns about the conduct of the trial. The report 
may contain recommendations for consideration by the DSMB concerning whether to close the 
trial, report the results, or continue accrual or follow-up. 
The results of each DSMB meeting are summarized in a formal report sent by the DSMB Chair to 
the Group Chair and AMC ODMC. The DSMB report contains recommendations on whether to 
close each study reviewed, whether to report the results, and whether to continue accrual or follow-
up. A primary recommendation (e.g., continue with no change; recommended or required 
modification; stop) must be included in the document. The Group Chair is then responsible for 
notifying the Protocol Chair and relevant Disease-oriented Working Group Chair before the 
recommendations of the DSMB are carried out. In the unlikely event that the Protocol Chair does 
not concur with the DSMB, then the NCI Division Director or designee must be informed of the 
reason for the disagreement. The Study Chair, relevant Disease-oriented Working Group Chair, 
Group Chair, DSMB Chair, and NCI Division Director or designee will be responsible for reaching 
a mutually acceptable decision about the study. CTEP approval of a formal amendment will be 
required prior to any implementation of a change to the study. 
Following a DSMB meeting, a summary of the serious adverse events reported to the DSMB is 
posted to the AMC web site. It is each site’s responsibility for conveying this information to its 
IRB. 
Plans for Assuring Compliance with Requirements Regarding the Reporting of Adverse 
Events (AE) 
For trials monitored by the NCI’s Clinical Data Update System (CDUS), adverse event 
information is transmitted electronically to NCI on a quarterly basis. For trials monitored by NCI’s 
Clinical Trials Monitoring Service (CTMS), adverse event information is transmitted 
electronically to NCI every two weeks. 
The Protocol Chair, AMC Group Chair, and the AMC ODMC share responsibility in assuring that 
participating investigators comply with the protocol requirements for adverse event reporting. All 
AMC investigators certify compliance with NCI and FDA requirements for adverse event 
reporting by signing the AMC Adherence Statement for site membership, the protocol signature 
page for each protocol active at the site, and Form FDA-1572 for CTEP investigator registration 
and IND studies sponsored by AMC investigators. Investigators are responsible for identifying 
and reporting all adverse events to the AMC ODMC, CTEP-AERS, and/or sponsors according to 

 
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the protocol requirements, and assuring compliance with reporting to the local IRB. Protocol 
compliance with adverse event reporting requirements is assessed by the AMC ODMC during 
routine site audits by reviewing the site’s source documentation.  
The data entry system used for AMC studies, AdvantageEDC/Advantage eClinical (a web-based 
data entry and enrollment system), is programmed to notify the site investigator, protocol chair, 
AMC Medical Monitor, and AMC ODMC via email in the event that a site reports an adverse 
event that meets expedited reporting criteria to NCI and/or FDA. If the site does not follow with 
an expedited report, the AMC ODMC contacts sites to request compliance with reporting 
requirements. Additionally, the protocol chair, AMC ODMC, and the AMC Medical Monitor 
review reported adverse events on a routine basis to identify adverse events reported by sites that 
require expedited reporting. The Protocol Chair, AMC Group Chair, and IND sponsors have 
general oversight for assuring that routine and expedited adverse reporting requirements are met 
by the responsible parties. 
Plans for Assuring that any Action Resulting in a Temporary or Permanent Suspension of 
an NCI-Funded Clinical Trial is Reported to the NCI Grant Program Director Responsible 
for the Grant 
In the event that termination of the trial or major modification to the protocol is under 
consideration, the Protocol Chair will convene the AMC Data Coordinator and Disease-oriented 
Working Group Chair by conference call to discuss the options. For phase I and II trials, the 
Protocol Chair also has the option of asking the DSMB to review the study. The AMC ODMC will 
inform the CTEP Protocol Information Office (PIO) when studies are temporarily or permanently 
closed. The Cancer Treatment and Evaluation Program (CTEP) of the National Cancer Institute 
(NCI) must approve all protocol amendments prior to distributing to the AMC sites. 
Plans for Assuring Data Accuracy and Protocol Compliance 
All study data for AMC clinical trials are entered directly by AMC clinical site staff into 
AdvantageEDC/Advantage eClinical. During data entry, the system performs validation checks on 
many fields and performs consistency checks between select fields. Range checks are placed on 
each field to eliminate entry of out-of-range values. Edit check programs are run on the database 
on a set schedule to identify and resolve inconsistencies between forms or data collected at 
different points in time. AMC ODMC staff routinely interacts with site staff to resolve any data 
problems. 
In accordance with NCI guidelines, the AMC ODMC conducts audits at the AMC sites to evaluate 
compliance with regulatory issues, and to review data for specific cases by checking source 
documents. These reports are sent to the site Principal Investigator and to the NCI. In the event 
that major violations are identified, sites are asked to provide a written corrective and preventative 
action plan to correct deficiencies. If needed, a repeat site audit is conducted. In the event that a 
site does not correct deficiencies in a pre-determined time frame, the AMC Executive Committee 
has the option of taking action against the site. Possible actions include, but are not limited to, 
suspending enrollment of new patients to AMC trials until deficiencies are corrected; 
recommending a decrease in funding to the site; and requiring specific training for site 
investigators or staff members. 

 
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APPENDIX IX: MANAGEMENT OF ABNORMAL CYTOLOGY AND HISTOLOGY 
Cervical Cytology 
Women with an ASC-US cytology test of the cervix will undergo reflex HPV testing as is standard 
of care. Referral to colposcopy will be made if the HPV test is “positive.” 
Referral for colposcopic evaluation is recommended for cervical cytology of LSIL, HSIL, ASC-H 
and atypical glandular cells. 
Anal Cytology 
Anal cytology of ASC-H/HSIL+ should be further evaluated by HRA within three to six months 
of the cytology results. If a concurrent HRA (at visits 1, 3, and 5) does not identify anal HSIL, the 
HRA (and anal cytology) should be repeated within three to six months. 
Management of anal HSIL 
Management/treatment options for anal HSIL are up to the discretion of the Principal Investigator 
at each site. 

 
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APPENDIX X: ACSR SPECIMEN PREPARATION AND SHIPPING INSTRUCTIONS 
A. 
GENERAL 
All specimens for ACSR donation will be shipped according to these instructions. To 
ship blood specimens, use a diagnostic shipper approved for a volume of at least 30 cc. The 
use of the SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. These 
shippers may be ordered at the SAF-T-PAK website www.saftpak.com. The following 
instructions below are for use with the recommended STP-210 shipper. If using another 
federally approved diagnostic shipper, please follow instructions provided for that specific 
shipper. 
NOTE: Specimens MUST BE SHIPPED Monday through Wednesday as an 
OVERNIGHT PRIORITY shipment. Specimens are NOT ACCEPTED ON FRIDAYS, 
SATURDAYS, OR SUNDAYS in the GWU/ACSR Lab. 
B. 
SPECIMEN PREPARATION, PACKAGING, AND SHIPMENT 
BLOOD SPECIMENS 
Draw two 8.5 cc (ml) yellow top (acid citrate dextrose [ACD] solution A) tubes of blood 
from study participant. With a black, water resistant, sharpie pen, label each specimen with 
the following information: 
• AMC Protocol # 084 
• AMC Participant ID#  
• Date and time of collection  
• Specimen type, i.e., WB=Whole Blood, P=Plasma, S=Serum, or Tissue 
• Specimen purpose: Donation 
Specimen Shipment 
1) Seal the tops of the 8.5 cc yellow top tubes with parafilm. 
2) Place the two sealed tubes into bubble wrap (provided in STP-210 kit). 
3) Tape around the bubble wrap so that the roll stays together and the tubes cannot fall 
out or break. 
4) Place absorbent material sheet around the bubble wrapped tubes and slip into a 
biohazard poly-bag and “self-seal.” 
5) Place poly-bag containing tubes into the white TYVEK bag and seal. 
6) Place the TYVEK bag into the STP-210 diagnostic cardboard shipper. Seal the 
cardboard shipper with clear packing/shipping tape. 
7) Affix the FED-EX airbill on blank side of the shipper making sure that it is marked 
“FED-EX PRIORITY OVERNIGHT.” 
8) Mark “OTHER” in the airbill under “Packaging.” Please use FedEx #: 352207845. 
9) Under airbill section “Special Handling,” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 
10) Place “From/To” information onto areas provided on the shipper. 
Blood specimens should be shipped by overnight express at room temperature to: 
Dr. Sylvia Silver 
GW Biorepository 

 
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George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: (202) 994-2945 
Fax: (202) 994-5056 
11) Make certain that shipper is already either pre-labeled with the “UN#3373” stamp, or 
make a paper label with “UN#3373” and affix it to the shipper. 
12) Make certain that the net volume of the specimen being shipped is written in the space 
provided on the shipper or make a separate label with the volume in ml and affix to the 
shipper. 
13) Affix airbill to shipper so that the ‘UN’ and ‘VOLUME’ labels are visible. 
14) RETAIN THE TOP COPY OF THE AIRWAY BILL FOR YOUR RECORDS. 
15) Place the box in the FedEx pickup area at your site or call to request a package pickup. 
Please Note: The shippers will be mailed back to each AMC site. 
INSTRUCTIONS FOR BLOOD SPECIMENS COLLECTED ON THURSDAY OR 
FRIDAY: 
Preparation of Plasma and Mononuclear Cells 
Refer to the ACSR’s SOP on Separation of Plasma and Mononuclear Cells on the AMC 
Operations web site for instructions on preparing plasma and PBMC aliquots. It is 
preferable that separation occurs as soon as possible. If necessary, whole blood in ACD 
(yellow top tubes) can be held at room temperature for no more than 24 hours. 
Freeze the cell suspension in 0.5 ml aliquots in sterile NUNC vials by placing the NUNC 
tubes in a room temperature, alcohol saturated, control rate freezer container, and store in 
the -80°C freezer overnight. Transfer the cell suspension into the liquid nitrogen 
temperature freezer for long-term storage the next working day. 
***PLEASE DOUBLE CHECK PACKAGING OF SHIPPER AND DO NOT 
DEVIATE FROM REQUESTED LABELING. Shipping frozen aliquots requires the 
use of packaging acceptable for dry ice and Class 9 label with weight of dry ice written 
on package. 
C. 
RECORD OF SPECIMENS 
This study will track specimens via GlobalTraceSM, a component of the AMC 
AdvantageEDCSM system. The GlobalTraceSM shipment manifest must accompany all 
specimen shipments. 

 
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APPENDIX XI: RESIDUAL CYTOLOGY SPECIMEN HANDLING AND SHIPPING 
GENERAL 
If the participant consents to the donation of excess AMC-084 study specimens to the AMC 
Biorepository (described in the model Informed Consent form), residual cytology media 
from local anal and cervical cytology readings will be submitted to the AMC Biorepository. 
Prior to shipment, store all residual specimens from local anal and cervical liquid cytology readings 
at 2-8°C. Specimens must be shipped to the AMC Biorepository within 4 weeks of collection.  
NOTE: Specimens MUST BE SHIPPED Monday through Wednesday on ice packs using 
PRIORITY OVERNIGHT service. Specimens are NOT ACCEPTED ON FRIDAYS, 
SATURDAYS, OR SUNDAYS at the AMC Biorepository at GWU. 
Ship the Specimens to:  
Dr. Sylvia Silver 
GW Biorepository 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: (202) 994-2945 
Fax: (202) 994-5056 
Liquid Cytology Residual Sample Labeling 
Samples must be labeled with the bar-coded labels provided. Each sample should be labeled with 
the following information: 
Participant ID: “084-XXX-XXX” 
Specimen Type: "Anal Cytology Medium” or “Cervical Cytology Medium” 
Specimen Medium: “Surepath” “ThinPrep” 
Specimen Purpose: “ACSR donation” 
Date of Sample Collection: MM/DD/YYYY 
Shipping Instructions 
To ship anal and cervical residual specimens, use a diagnostic shipper approved for a volume of 
at least 30 cc. The use of the SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. 
These shippers may be ordered at the SAF-T-PAK website www.saftpak.com. The following 
instructions below are for use with the recommended STP-210 shipper. If using another federally 
approved diagnostic shipper, please follow instructions provided for that specific shipper. Use 
FedEx account #: 352207845. 
RECORD OF SPECIMENS 
This study will track specimens via GlobalTraceSM, a component of the AMC AdvantageEDCSM 
system. The GlobalTraceSM shipment manifest must accompany all specimen shipments. 

 
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APPENDIX XII: INFORMED CONSENT FOR OPTIONAL ACSR DONATION 
Study Title for Study Participants: 
Collecting Blood and Tissue Sample Donations for 
Research for HIV/AIDS-Related Cancers 
Official Study Title: 
Biospecimen Collection and Donation to the AIDS  
and Cancer Specimen Resource (ACSR) 
What is the usual approach to donate blood and/or tissue to the ACSR? 
You are being asked to donate blood and/or tissue for research. You are being asked to take part 
in this study because you have HIV infection and have been offered participation in an AMC 
clinical trial. The AMC works with the ACSR to collect donated samples from persons with HIV 
infection for research studies. People who do not take part in an AMC clinical trial can also donate 
samples to the ACSR. 
What are my other choices if I do not take part in this study? 
It is your choice to donate or not donate your blood and/or tissue samples. You may still take part 
in the AMC clinical study if you choose not to donate blood or biopsy samples. You may also 
choose to donate: 
• Blood but not tissue, or  
• Tissue but not blood. 
What is the AIDS and Cancer Specimen Resource (ACSR)? 
The National Cancer Institute (NCI) has set up the ACSR. The ACSR is a biorepository (bank) 
that collects human biological specimens (biospecimens) from persons who have HIV, HIV-
related conditions, or AIDS-related cancers. The ACSR stores the samples and some of the donor’s 
medical information for use in future research studies. 
The ACSR has an independent research panel that approves researchers’ study plans to use the 
ACSR’s stored samples. The ACSR only gives samples and medical information to researchers 
after approving their projects. Researchers may use the biospecimens to study cancers and other 
diseases associated with HIV disease. This information may help us learn more about the causes 
of treat HIV-related diseases and cancers and to develop better ways to screen, diagnose, and treat 
them. 
Why is this study being done? 
The purpose of this study is to collect biospecimens for the ACSR. Researchers may study samples 
from the ACSR in combination with hundreds or thousands of other samples to explore how 
genetic factors may be related to HIV-related diseases and cancer. The information might help 
doctors in the future to identify who will or will not benefit from treatment. The samples may be 
used to learn more about how HIV-related diseases and cancers develop. The samples may also 
lead to new tests or discoveries. Finally, scientists may use the samples to study the genetic 
material from your cancer tissue and compare it to the material from your normal tissue (blood) to 
try to find the differences that exist. These studies could make it possible to identify many of the 
changes that are associated with diseases such as cancers. It may also help us tailor treatments to 
a patient's unique genetic make-up and/or to the genetic markers of the tumors. 
 
 

 
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What extra tests and procedures will I have if I take part in this study? 
1) If you agree to donate blood, the medical team will draw about 2 tablespoons of blood to give 
to the ACSR. This takes about 10 minutes. 
2) If you agree to donate tissue, your leftover tissue biopsy material will be donated to and stored 
by the ACSR. If it turns out that your study doctor needs more of your tissue for additional 
studies, the ACSR will return all of your tissue back to your study doctor. 
3) Some of your clinical information will be released to the ACSR and entered into their database. 
The information given to the ACSR will not include your name or any information that could 
personally identify you. 
No extra biopsies will be collected for the ACSR. We will only give tissue that is left over after 
making decisions about your treatment or diagnosis to the ACSR. The study doctor will not take 
any extra biopsies just for the ACSR. 
We cannot tell you right now what future research these samples would be used for. Instead, we 
are asking that you give approval to give your samples for future testing without contacting you 
again. The results of whatever research is done on your samples will not be told to you or your 
doctor. The results of the tests will not be placed in your study records. 
How long will ACSR keep my samples? 
Your blood and/or tissue sample will be stored until it is used for research. The samples may be 
stored indefinitely. 
What possible risks can I expect from taking part in this study? 
• Blood Draw: The risks of drawing blood include temporary discomfort from the needle stick, 
bruising, and, rarely, infection. 
• Biopsy: The risks of biopsy include possible need for stitches depending on the size of the 
biopsy. There may be swelling, slight pain and a small amount of blood loss. There is also a 
chance of infection at the site of the biopsy.  
• Confidentiality: While the ACSR and researchers who study ACSR samples will have no 
information that could identify you, there is a risk that someone could use information from 
genetic studies to trace your samples back to you. The researchers believe the chance that 
someone will identify you is very small, but the risk may change in the future as people come 
up with new ways of tracing information. In some cases, this information could be used to 
make it harder for you to get or keep a job. There are laws against misuse of genetic 
information, but they may not give full protection. The researchers believe the chance these 
things will happen is very small, but cannot promise that they will not occur. 
• There can also be a risk in finding out new genetic information about you. New health 
information about inherited traits that might affect you or your blood relatives could be found 
during a study. 
Let your study doctor know of any questions you have about these possible risks. You can ask 
the study doctor questions about side effects at any time. 
 

 
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What possible benefits can I expect from taking part in this study? 
This study is unlikely to help you. This study may help us learn things that may help people in the 
future. 
The information may help to identify those who are at increased risk and those who may benefit 
from targeted treatment and screening. In turn, these studies could help find ways to prevent or 
improve treatments for HIV-related diseases and AIDS-related cancers. 
Can I stop taking part in this study? 
Yes, you may withdraw your samples from the ACSR at any time while you are taking part in the 
main study. We will not keep information that links you to your samples after the main study is 
over. After the study is over, the AMC and the ACSR will not be able to identify your specific 
samples. Contact the contact your AMC study coordinator if you choose to stop taking part. The 
coordinator can ask the ACSR to remove your sample and clinical information from the ACSR. 
However, if any research has already been done using some of your samples, the data will be kept 
and analyzed as part of those studies. 
What are my rights in this study? 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 
rights. 
For questions about your rights while in this study, call the ________________________ (insert 
name of center) Institutional Review Board at __________________ (insert telephone number). 
(Note to Local Investigator: Contact information for patient representatives or other individuals 
at a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can also be listed here.) 
What are the costs of taking part in this study? 
There will be no cost to you for donating your samples to the ACSR. You will not be paid for 
taking part in this study. 
What happens if I am injured or hurt because I took part in this study? 
If you are injured or hurt as a result of taking part in this study and need medical treatment, please 
tell your study doctor. The AMC will not offer to pay for medical treatment for injury. Your 
insurance company may not be willing to pay for study-related injury. If you have no insurance, 
you would be responsible for any costs. 
If you feel this injury was a result of medical error, you keep all your legal rights to seek payment 
for injury even though you are in a study. 
Who will see my medical information? 
Your privacy is very important to us and the researchers will make every effort to protect it. Your 
information may be given out if required by law. For example, certain states require doctors to 
report to health boards if they find a disease like tuberculosis. However, the researchers will do 
their best to make sure that any information that is released will not identify you. Some of your 
health information, and/or information about your specimen, from this study will be kept in a 
central database for research. Your name or contact information will not be put in the database. 

 
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There are organizations that may inspect your records. These organizations are required to make 
sure your information is kept private, unless required by law to provide information. Some of these 
organizations are: 
• The AIDS Malignancy Consortium (AMC) 
• The Institutional Review Board, IRB, is a group of people who review the research with the 
goal of protecting the people who take part in the study. 
• The Office for Human Research Protections and the National Cancer Institute in the U.S. 
To protect your privacy, the AMC does not keep identifying information that links study 
participants to specific samples. As a result, the AMC and ACSR will not be able to link the results 
from studies that use your samples back to you. Thus, information, including genetic information, 
that researchers may obtain in studies that use your biospecimens may not be directly linked to 
you and will not be placed in your medical record. However, some clinical and basic information 
obtained confidentially from the AMC will be attached with these data. It is possible that findings 
may one day help, for example, people of the same race or sex as you. It also is possible that 
genetic factors might come to be associated with people who have HIV and cancer through these 
kinds of studies. 
Where can I get more information? 
You may visit the NCI Web site at http://cancer.gov/ for more information about studies or general 
information about cancer. You may also call the NCI Cancer Information Service to get the same 
information at 1-800-4-CANCER (1-800-422-6237). 
Who can answer my questions about this study? 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries. Contact the study doctor __________________ (insert name of study 
doctor[s]) at __________________ (insert telephone number). 
Please circle your answer to show whether or not you would like to take part in each option: 
1. I agree to donate my blood to the ACSR for future research that may be used to learn 
about, prevent, diagnose, or treat HIV-related diseases and cancer. 
YES 
 
NO 
2. I agree to donate my blood to the ACSR for future research that may include genetic 
testing to learn about, prevent, diagnose, or treat HIV-related diseases and cancer.  
YES 
 
NO 
3. I agree to donate some of my tissue biopsy material that is not required for my treatment 
or diagnosis to the ACSR for future research that may be used to learn about, prevent, 
diagnose, or treat HIV-related diseases and cancer. 
YES 
 
NO 
4. I agree to donate some of my tissue biopsy material to the ACSR for future research that 
may include genetic testing to learn about, prevent, diagnose, or treat HIV-related 

 
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diseases and cancer.  
YES 
 
NO 
My Signature Agreeing to Take Part in the Study 
I have read this consent form or had it read to me. I have discussed it with the study doctor and my 
questions have been answered. I will be given a signed copy of this form. I agree to take part in 
the optional study.  
 
____________________________________ 
___________________________________ 
Participant’s Signature 
 
 
 
Date of Signature 
 
____________________________________ 
___________________________________ 
Signature of Person(s) conducting the 
 
Date of Signature 
Informed Consent Discussion 

 
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APPENDIX XIII: BASELINE PARTICIPANT QUESTIONNAIRE 
Screening HIV-Infected Women for Anal Cancer Precursors–Visit 1 
 
Participant ID: 084 - __ __ __ - __ __ __ 
 
Date of administration: __ __ / __ __ / __ __ __ __ 
 
Administered by: ____________________________ 
 
Location of administration (e.g., clinic or telephone): ___________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thank you for agreeing to speak with me today. 
 
I will be asking some questions about your health and some personal questions. If you feel 
uncomfortable answering any question or want to stop at any time, just let me know.

 
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CURRENT HEALTH STATUS (EQ-5D-5L) 

 
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10 
0 
20 
30 
40 
50 
60 
80 
70 
90 
100 
5 
15 
25 
35 
45 
55 
75 
65 
85 
95 
The best health 
you can imagine 
The worst health  
 you can imagine 

 
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To begin, I will ask some general health questions.  
 
• We would like to know how good or bad your health is TODAY. 
• This scale is numbered from 0 to 100. 
• 100 means the best health you can imagine. 
• 0 means the worst health you can imagine. 
• Mark an X on the scale to indicate how your health is TODAY. 
• Now please write the number you marked on the scale in the box below 
 
 
 
1. YOUR HEALTH TODAY =  
 
 

 
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Please tell me which one of these statements best describes your health today (repeat for each 
section). Under each heading, please tick the ONE box that best describes your health TODAY. 
2. MOBILITY: 
I have no problems in walking about. 
1 
 
I have slight problems in walking about. 
2 
 
I have moderate problems in walking about. 
3 
 
I have severe problems in walking about. 
4 
 
I am unable to walk about. 
5 
 
3. SELF-CARE: 
I have no problems washing or dressing myself. 
1 
 
I have slight problems washing or dressing myself. 
2 
 
I have moderate problems washing or dressing 
myself. 
3 
 
I have severe problems washing or dressing myself. 
4 
  
I am unable to wash or dress myself. 
5 
 
4. USUAL ACTIVITIES (e.g., work, study, housework, family, or leisure activities): 
I have no problems doing my usual activities.  
1 
 
I have slight problems doing my usual activities. 
2 
 
I have moderate problems doing my usual activities. 
3 
 
I have severe problems doing my usual activities. 
4 
 
I am unable to do my usual activities. 
5 
 
5. PAIN/ DISCOMFORT: 
I have no pain or discomfort. 
1 
 
I have slight pain or discomfort. 
2 
 
I have moderate pain or discomfort. 
3 
 
I have severe pain or discomfort. 
4 
 
I have extreme pain or discomfort. 
5 
 
6. ANXIETY/ DEPRESSION: 
I am not anxious or depressed. 
1 
 
I am slightly anxious or depressed. 
2 
 
I am moderately anxious or depressed. 
3 
 
I am severely anxious or depressed. 
4 
 
I am extremely anxious or depressed. 
5 
 
ANXIETY AND DEPRESSION [PHQ-4] 
The following answer choices are: “not at all”; “several days”; “more days than not”; “nearly every 
day”; and “don’t know”.  

 
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7. Over the past 2 weeks have you been bothered by these problems? 
 
Not at all 
Several 
days 
More 
days than 
not 
Nearly 
every 
day 
Don’t 
know 
Feeling nervous, anxious, or 
on edge 
0 
1 
2 
3 
98 
Not being able to stop or 
control worrying 
0 
1 
2 
3 
98 
Feeling down, depressed, or 
hopeless 
0 
1 
2 
3 
98 
Little interest or pleasure in 
doing things 
0 
1 
2 
3 
98 
PAST PAIN EXPERIENCE 
These next questions are about pain. 
Using the FACES Pain Rating Scale, please tell me how much pain you have experienced in the 
past for the following. 
8. Toothache 
No hurt 
Hurts  
little bit 
Hurts 
little 
more 
Hurts 
even 
more 
Hurts 
whole lot 
Hurts 
worst 
Not 
applicable 
0 
2 
4 
6 
8 
10 
97 
9. Menstrual Period Pain 
No hurt 
Hurts  
little bit 
Hurts 
little 
more 
Hurts 
even 
more 
Hurts 
whole lot 
Hurts 
worst 
Not 
applicable 
0 
2 
4 
6 
8 
10 
97 
10. Cervical Pap Smear 
No hurt 
Hurts  
little bit 
Hurts 
little 
more 
Hurts 
even 
more 
Hurts 
whole lot 
Hurts 
worst 
Not 
applicable 
0 
2 
4 
6 
8 
10 
97 
SEXUAL BEHAVIORS AND SEXUAL HISTORY 
Contact during sex is an important way in which some women get abnormalities on the cervix and 
anus. We need your help in understanding how women's behavior can affect their health. For this 
reason, it is very important for you to answer some questions about your personal sexual behavior. 
Each question will specify the type of sex to which we refer. Please consider any sexual 
experiences, even sex that was upsetting or involuntary such as rape. 

 
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We assure you that your answers will be kept confidential. By providing this information, you will 
help us a great deal with this study. 
Please listen to each question carefully and answer as honestly as possible, even if you only had 
that type of sexual experience one time. Although some of the behaviors or sexual practices we 
ask about may be new to you, they are far more common than you may think. 
11. Have you ever experienced sexual assault? 
Response 
Code 
Yes 
1 
No 
2 
I don’t know 
98 
Decline to answer 
99 
Sex with Men 
The next questions refer only to vaginal sex with men. This is when a man puts his penis, fingers 
or a sex toy/object in a woman’s vagina. 
12. Have you ever, any time in your life, had vaginal sex with a man? 
No 
(skip to question 16) 
Yes 
Decline to answer 
(skip to question 16) 
0 
1 
99 
13. How many different men have you had vaginal sex with in your entire life?  
None 
1 
2-5 
6-10 
More than 
10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
14. How many men have you had vaginal sex with in the past 6 months? 
None 
1 
2-5 
6-10 
More than 
10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
15. How often were condoms used to cover the man’s penis, sex toy or object when you had 
vaginal sex with a man in the past 6 months? 
Never 
Rarely 
Sometimes 
but less 
than half 
About 
half the 
time 
More 
than half 
the time 
Every 
time 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 
Now I am going to ask you questions about anal sex with a man. This is when a man puts his penis, 
finger, sex toy or object in your anus.  
 
 

 
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16. Have you ever, any time in your life, had anal sex with a man?  
No 
(skip to question 22) 
Yes 
Decline to answer 
(skip to question 22) 
0 
1 
99 
17. When was the last time a man put his penis in your anus? 
Within the 
past week 
Within 
the past 
month 
Within the 
past 6 
months 
Within 
the past 
year 
Over one 
year ago 
Unsure 
Decline to 
answer 
1 
2 
3 
4 
5 
98 
99 
18. How many different men have you had anal sex with in your entire life?  
None 
1 
2-5 
6-10 
More than 10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
19. How many men have you had anal sex with in the past 6 months? 
None 
1 
2-5 
6-10 
More than 10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
20. How often did you have anal sex with a man in the past 6 months? 
Never 
Less than 1 
time/month 
1-3 
times/ 
month 
Once/ 
week 
2-6 
times/ 
week 
Daily 
Unsure 
Decline 
to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 
21. How often was a condom used to cover the man’s penis, finger, sex toy or object when you 
had anal sex with a man in the past 6 months? 
Never 
Rarely 
Sometimes 
but less 
than half 
About half 
the time 
More than 
half the 
time 
Every 
time 
Unsure 
Decline 
to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 

 
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SEXUALLY TRANSMITTED INFECTIONS  
The following questions ask about infections and diseases that are sexually transmitted. Once 
again, I assure you that your answers will be kept confidential. 
Please let us know if you have ever been diagnosed with or treated for any of the infections we ask 
about now. 
22. Have you ever had anal warts? These are warts inside or around your anus. 
No 
Yes, in the past 
6 months 
Yes, but longer 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
23. Have you ever had warts inside your vagina, on the vulva, or in both places?  
No 
Inside 
Outside 
Both 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
98 
99 
24. Have you ever had herpes around the vagina or anus? These are painful blistering sores around 
your private parts. 
No 
Yes, in the past 
6 months 
Yes, but more 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
25. Have you ever had Chlamydia? This is an infection transmitted during sexual contact. 
No 
Yes, in the 
past 6 months 
Yes, but more 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
26. Have you ever had Gonorrhea (“clap”)? This is an infection transmitted during sexual 
contact. 
No 
Yes, in the 
past 6 months 
Yes, but more 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
27. Have you ever had pelvic inflammatory disease (PID) or infection of your fallopian tubes 
or ovaries? 
No 
Yes, in the 
past 6 months 
Yes, but more 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
 
 
 

 
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28. Have you ever had syphilis? This is an infection transmitted during sexual contact. (The 
treatment is weekly painful penicillin shots.) 
No 
Yes, in the 
past 6 months 
Yes, but more 
than 6 months ago 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
2 
98 
99 
CERVICAL CANCER SCREENING HISTORY 
29. Have you ever had an abnormal Pap smear result when screened for cervical cancer? 
No  
(skip to question 32) 
Yes 
Unsure/ 
Don’t know 
0 
1 
98 
30. Did you have colposcopy after the abnormal Pap smear? 
No  
(skip to question 32) 
Yes 
Unsure/ 
Don’t know 
0 
1 
98 
31. If you had colposcopy, did you have any treatment after the colposcopy? 
No  
(skip to question 32) 
Yes 
Unsure/ 
Don’t know 
0 
1 
98 
PRE-PROCEDURE EXPLANATION AND QUESTIONS [Acceptability] 
In addition to the previous questions, you have consented to have some procedures done today for 
this study. These procedures are an anal Pap smear, high resolution anoscopy, and a biopsy of any 
abnormal tissue or area that is seen.  
Please tell me if you have any of the following concerns about having the following 
examinations or procedures. For each of these statements, please tell me whether you agree or 
disagree. Then you will be asked if you slightly or strongly agree/disagree with the statement. 
 
 

 
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32. ANAL PAP SMEAR 
An anal Pap smear will be taken. This is like a cervical Pap smear. A Q-tip type swab will be 
inserted into the anus by the doctor or nurse practitioner to obtain cells that will be sent to the 
laboratory to check for abnormalities. 
33. HIGH RESOLUTION ANOSCOPY 
High resolution anoscopy is done with use of a plastic tube instrument inserted in the anus to 
look at the tissue under a special light to see if there are warts or other abnormalities in the anal 
area. Vinegar is used to make any abnormal areas show up better under the light. 
Any abnormalities seen will be biopsied, or removed, with a small cutting instrument to send 
to the laboratory for special analysis. 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I am concerned about 
pain. 
1 
2 
3 
4 
5 
99 
I feel the exam will be 
uncomfortable. 
1 
2 
3 
4 
5 
99 
I feel at ease. 
1 
2 
3 
4 
5 
99 
I am prepared to have 
the procedure. 
1 
2 
3 
4 
5 
99 
34. Which of the following examinations or procedures concerns you the very most today? 
(Choose one) 
Code 
Procedure 
0 
No Concern 
1 
Anal Pap smear 
2 
High resolution anoscopy 
3 
Possible biopsy 
99 
Decline to answer 
 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I am concerned about 
pain. 
1 
2 
3 
4 
5 
99 
I feel the exam will be 
uncomfortable. 
1 
2 
3 
4 
5 
99 
I feel at ease. 
1 
2 
3 
4 
5 
99 
I am prepared to have 
the procedure. 
1 
2 
3 
4 
5 
99 

 
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HEALTH BEHAVIOR QUESTIONS 
Now I am going to ask you a few questions about yourself.  
[from ACTG self report, questions E, H, QL0742(A5257)/ 12-31-08] 
35. Are you on HIV medication(s)? 
 
 
 
36. 
Rate your ability to take all of your HIV medications as specifically prescribed. 
Very 
poor 
Poor 
Fair 
Good 
Very 
good 
Excellent 
N/A 
Unsure/ 
Don’t know 
Decline to 
answer 
1 
2 
3 
4 
5 
6 
97 
98 
99 
SMOKING QUESTIONS  
37. Altogether, have you smoked at least 100 or more cigarettes in your entire lifetime? 
INTERVIEWER NOTE: IF NECESSARY: 5 packs = 100 cigarettes 
No  
(skip to question 40) 
Yes 
Unsure/Don’t know 
(skip to question 40) 
Decline to answer 
0 
1 
98 
99 
 
Ask former and current smokers the following questions: 
38. When you were smoking most heavily, how many cigarettes did you smoke on an average 
day? (1 pack = 20 cigarettes) 
_______ Cigarettes per day 
39. For how long did you smoke this heavily? (If time unit is known, indicate the number of years.) 
Code 
Years 
98 
Unknown 
COST/TRANSPORTATION QUESTIONS 
No  
(skip to question 37) 
Yes 
Unsure/Don’t know 
(skip to question 37) 
0 
1 
98 

 
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40. What is the main source of your financial support, including food, rent, and other expenses? 
(Check participant's response. If more than one choice given, PROBE: Is one of these the most 
important source of your income? If participant answers "No," record all responses given) 
Response 
Code 
Own job or salary. 
1 
Someone else's job or salary (Specify relationship):_______________________ 
) 
2 
Public assistance, e.g., AFDC, SSI, food stamps 
3 
Other (Specify): __________________________ ) 
8 
Unknown 
98 
41. Which one best describes your hourly wage or annual income? 
Hourly Wage  
Annual Income 
$0.00 - $4.99 
$0.00 - $9,999 
$5.00 - $7.25 
$10,000 - $14,999 
$7.26 - $9.99  
$15,000 - $19,999 
$10.00 - $14.99 
$20,000 - $29,999 
$15.00 - $19.99 
$30,000 - $39,999 
$20.00 - $24.99 
$40,000 - $49,999 
$25.00 - $29.99 
$50,000 - $59,999 
$30.00 - $34.99 
$60,000 - $69,999 
$35.00 - $39.99 
$70,000 - $79,999 
$40.00 - $49.99 
$80,000 - $99,999 
More than $50.00/hour 
More than $100,000/year 
42. Did you miss work today for this visit? 
No 
Yes 
Not 
applicable/Don’t 
Work 
0 
1 
99 

 
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43. How did you get to the clinic today? 
Response 
Code 
Drive yourself 
1 
Get a ride from someone else in a personal vehicle 
2 
Take public transportation such as the metro bus or metro rail 
3 
Take a taxi 
4 
Walk or ride bike, or 
5 
Get there some other way (SPECIFY) ____________ 
6 
Decline to answer 
99 
44. If you took private/public transportation, what was the fare? 
$__________________ 
45. How much time (including travelling time) will you miss from your usual activities because 
of this appointment? 
Response 
Code 
Less than 15 minutes 
1 
15 to 30 Minutes  
2 
31 Minutes to 60 Minutes (1 Hour) 
3 
61 Minutes to 90 Minutes  
4 
91 Minutes to 120 Minutes (2 Hours) 
5 
120 Minutes to 180 Minutes (2 to 3 Hours) 
6 
180 Minutes to 240 Minutes (3 to 4 Hours) 
7 
240 Minutes to 300 Minutes (4 to 5 Hours) 
8 
300 Minutes to 360 Minutes (5 to 6 Hours) 
9 
More than 360 Minutes (More than 6 Hours) 
10 
46. How far did you travel for this appointment? 
_______miles 
47. If you drove, how much do you expect to pay for the parking? $___________ 
NA 
99 

 
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48. If you are accompanied to your appointment by someone who missed work, what is the gender 
and age of this person?  
Accompanied 
Not 
accompanied 
Male 
Female 
Age 
0 
1 
2 
 
49. Did you have to get a caretaker today to attend to your children and/or an adult person living 
in your household in order to come to your appointment? 
No 
(Skip to question number 53) 
Yes 
0 
1 
50. How much do you expect to pay the caretaker for today? (If no payment, skip to question 51) 
$_________ 
51. Did the caretaker miss work in order to help you?  
No  
(Skip to question number 52) 
Yes 
0 
1 
52. What is the gender and age of the caretaker? 
Male 
Female 
Age 
1 
2 
 
DEMOGRAPHIC QUESTIONS 
53. What is your marital status? 
Response 
Code 
Married 
1 
Not married, living with someone 
2 
Divorced/separated 
3 
Widowed 
4 
Single/never married 
5 
Other: (specify)_______________________  
6 
Decline to answer 
99 
54. What is your country of origin (where were you born)?  
Response 
Code 
United States of America 
1 
United States territory–Puerto Rico 
2 

 
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Haiti 
3 
Cape Verde 
4 
Uganda 
5 
Nigeria 
6 
Cameroon 
7 
Kenya 
8 
Mexico 
9 
Other Latin America (specify) 
10 
Other Africa (specify) 
11 
Other: 
(specify)________________________ 
99 
55. If you were born outside the United States, what age were you when you first came to live in 
the United States? 
Enter Age in Years 
N/A 
Unsure/Don’t know 
Decline to answer 
 
97 
98 
99 
56. What is the last grade (highest level) of school that you completed? 
Grade 
Code 
8th grade or less 
1 
Some high school 
2 
High school diploma 
3 
Some college or vocational school 
4 
Associate degree 
5 
College (4 year) degree 
6 
Graduate or professional degree 
7 
Don’t know 
98 
Decline to answer 
99 

 
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APPENDIX XIV: POST-PROCEDURE TELEPHONE FOLLOW-UP QUESTIONNAIRE 
AND SCRIPT 
Screening HIV-Infected Women for Anal Cancer Precursors 
POST PROCEDURE QUESTIONS 
 
The following questions will be asked 2-5 weeks after the procedures have been completed via a 
telephone follow up call, or a visit if preferred by the participant and/or investigator.  
 
Participant ID: 084 - __ __ __ - __ __ __ 
 
Date of administration: __ __ / __ __ / __ __ __ __ 
 
Administered by: _________________________ 
 
Location of administration (e.g. clinic or telephone): ___________________________________ 
 
Date of last study procedure visit: __ __ / __ __ / __ __ __ __ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thank you for agreeing to speak with me today.  
I will be asking some personal questions. Most of them are the same or similar to the original 
questions you answered previously. Again, if you feel uncomfortable answering any question or 
want to stop at any time, just let me know. 

 
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POST PROCEDURE QUESTIONS 
 
1. Did you have bleeding following the last HRA procedure? (If No, skip to question 4.) 
Response 
Code 
Yes 
1 
No 
2 
2. How many days did you have bleeding? ___________ days 
3. Did you feel the bleeding was: 
Response 
Code 
Mild 
1 
Moderate 
2 
Severe 
3 
4. Did you have pain following the last HRA procedure? (If No, skip to question 9.) 
Response 
Code 
Yes 
1 
No 
2 
5. How many days after the HRA procedure did you have pain? __________ days 
6. Did you feel the pain was: 
Response 
Code 
Mild 
1 
Moderate 
2 
Severe 
3 
7. Did you take any medication for the pain? (If no, skip to question 9.) 
Response 
Code 
Yes 
1 
No 
2 
8. And if so, what medication(s) 
Response 
Code 
Acetaminophen 
1 
NSAIDS 
2 
Narcotics 
3 
 

 
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9. Did you miss work because of bleeding or pain? (If no, skip to question 12.) 
Response 
Code 
Yes 
1 
No 
2 
10. If yes, was it because of the: 
Response 
Code 
Bleeding 
1 
Pain 
2 
Both 
3 
11. How many days did you miss work due to either bleeding or pain? 
__________ days 
12. Did you have any unscheduled visits to any healthcare provider because of bleeding or pain 
after the HRA? 
Response 
Code 
Yes 
1 
No 
2 
13. How many times have you had high resolution anoscopy (HRA)? (If only one time, skip to 
question 15.) 
Response 
Code 
1 time 
1 
2-4 times 
2 
5-10 times 
3 
More than 10 
4 
14. Comparing your experience with the first (or former) procedure to this most recent procedure, 
would you say that the most recent procedure was: 
Response 
Code 
Better 
1 
Same 
2 
Worse 
3 
I don’t know 
98 
 
 
 

 
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15. Before your recent HRA procedure, how informed were you about the purpose of HRA in 
screening for anal cancer? 
Response 
Code 
Well informed 
1 
Somewhat informed 
2 
Poorly informed 
3 
I don’t know 
98 
16. Before your recent HRA procedure, how informed were you about any discomfort that you 
could experience during the procedure? 
Response 
Code 
Well informed 
1 
Somewhat informed 
2 
Poorly informed 
3 
I don’t know 
98 
17. Before your recent HRA procedure, how informed were you about any discomfort/bleeding 
you might have after the procedure? 
Response 
Code 
Well informed 
1 
Somewhat informed 
2 
Poorly informed 
3 
I don’t know 
98 
18. Before your recent HRA procedure, how informed were you about self-care at home after the 
procedure? 
Response 
Code 
Well informed 
1 
Somewhat informed 
2 
Poorly informed 
3 
I don’t know 
98 
19. During your recent HRA procedure did you feel supported and well-cared for by the providers 
who performed the HRA? 
Response 
Code 
Yes 
1 
No 
2 
I don’t know 
98 

 
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20. Some people who have experienced sexual abuse, rape, or other trauma in their lives find the 
HRA procedure particularly distressing. Have you have had an experience such as these in 
your lifetime? (IF NO, go to question 22). 
Response 
Code 
Yes 
1 
No 
2 
I don’t know 
98 
21. IF YES, did your most recent HRA procedure cause you to remember the trauma?  
Response 
Code 
Yes 
1 
No 
2 
Not applicable 
97 
I don’t know 
98 
22. During your recent HRA procedure did you feel your privacy was respected? 
Response 
Code 
Yes 
1 
No 
2 
I don’t know 
98 
23. How likely would you be to follow recommendations to repeat the HRA procedures? 
Response 
Code 
Very unlikely 
1 
Somewhat unlikely 
2 
Neutral 
3 
Somewhat likely 
4 
Very likely 
5 
I don’t know 
98 
Please tell me your experience with each of the examinations or procedures. For each of these 
statements, please tell me whether you agree or disagree. Then you will be asked if you slightly 
or strongly agree/disagree with the statement. 
 
 

 
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24. Anal Pap smear 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I felt pain 
during the 
procedure. 
1 
2 
3 
4 
5 
99 
I felt 
uncomfortabl
e during the 
exam. 
1 
2 
3 
4 
5 
99 
I felt at ease. 
1 
2 
3 
4 
5 
99 
I was 
prepared to 
have the 
procedure. 
1 
2 
3 
4 
5 
99 
25. High resolution anoscopy 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I felt pain 
during the 
procedure. 
1 
2 
3 
4 
5 
99 
I felt 
uncomfortab
le during the 
exam. 
1 
2 
3 
4 
5 
99 
I felt at ease. 
1 
2 
3 
4 
5 
99 
I was 
prepared to 
have the 
procedure. 
1 
2 
3 
4 
5 
99 
26. Is there anything that will make getting the exam procedures the next time more comfortable 
for you? 
Response 
Code 
Yes 
1 
No (Questionnaire complete) 
2 
I don’t know 
98 
 
 

 
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27. Would any of the following make the next HRA procedure more comfortable for you? 
Response 
Yes 
No 
More explanation about what to expect from a health care 
provider. 
1 
2 
Medication to calm my nerves. 
1 
2 
More effective pain medication. 
1 
2 
Medication that will make me sleep during the procedure. 
1 
2 
28. If above answers were all no, but you feel there is something that would make the procedures 
more comfortable for you, please tell me what that would be: 
 
**AFTER COMPLETING QUESTIONNAIRE, PROVIDE THE PARTICIPANT THE 
RESULTS FROM HER PAP TESTS AND ANY BIOPSIES TAKEN, AND REVIEW ANY 
RECOMMENDATIONS FOR FOLLOW-UP.** 

 
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APPENDIX XV: FOLLOW-UP PARTICIPANT QUESTIONNAIRE 
Screening HIV-Infected Women for Anal Cancer Precursors 
FOLLOW-UP QUESTIONNAIRE FOR VISITS 2-5. 
 
Participant ID: 084 - __ __ __ - __ __ __ 
 
Date of administration: __ __ / __ __ / __ __ __ __ 
 
Administered by: ______________________________ 
 
Location of administration (e.g., clinic or telephone): ___________________________________ 
______________________________________________________________________________ 
 
Thank you for agreeing to speak with me today. 
I will be asking some personal questions—most of them are the same or similar to the original 
questions you answered 6 months ago. Again, if you feel uncomfortable answering any question 
or want to stop at any time, just let me know. 

 
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CURRENT HEALTH STATUS (EQ-5D-5L) 

 
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10
0 
20
30
40 
50
60
80
70
90
100 
5 
15
25
35
45
55
75
65
85
95
The best health 
 you can imagine 
The worst health 
 you can imagine 

 
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1. To begin, I will ask some general health questions.  
• We would like to know how good or bad your health is TODAY. 
• This scale is numbered from 0 to 100. 
• 100 means the best health you can imagine. 
• 0 means the worst health you can imagine. 
• Mark an X one the scale to indicate how your health is TODAY. 
• Now, please write the number you marked on the scale in the box below.  
 
 
YOUR HEALTH TODAY =  
 
 

 
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Please tell me which one of these statements best describes your health today (repeat for each 
section). Under each heading, please tock the ONE box that best describes your health TODAY. 
2. MOBILITY: 
I have no problems in walking about. 
1 
 
I have slight problems in walking about. 
2 
 
I have moderate problems in walking about. 
3 
 
I have severe problems in walking about. 
4 
 
I am unable to walk about. 
5 
 
3. SELF-CARE: 
I have no problems washing or dressing myself. 
1 
 
I have slight problems washing or dressing myself. 
2 
 
I have moderate problems washing or dressing myself. 
3 
 
I have severe problems washing or dressing myself. 
4 
 
I am unable to wash or dress myself. 
5 
 
4. USUAL ACTIVITIES (e.g., work, study, housework, family, or leisure activities): 
I have no problems doing my usual activities.  
1 
 
I have slight problems doing my usual activities. 
2 
 
I have moderate problems doing my usual activities. 
3 
 
I have severe problems doing my usual activities. 
4 
 
I am unable to do my usual activities. 
5 
 
5. PAIN/ DISCOMFORT: 
I have no pain or discomfort. 
1 
 
I have slight pain or discomfort. 
2 
 
I have moderate pain or discomfort. 
3 
 
I have severe pain or discomfort. 
4 
 
I have extreme pain or discomfort. 
5 
 
6. ANXIETY/ DEPRESSION: 
I am not anxious or depressed. 
1 
 
I am slightly anxious or depressed. 
2 
 
I am moderately anxious or depressed. 
3 
 
I am severely anxious or depressed. 
4 
 
I am extremely anxious or depressed. 
5 
 
ANXIETY AND DEPRESSION [PHQ-4] 
The following answer choices are: “not at all”; “several days”; “more days than not”; “nearly every 
day”; and “don’t know”.  
7. Over the past 2 weeks have you been bothered by these problems? 

 
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Not at all 
Several 
days 
More days 
than not 
Nearly 
every day 
Don’t 
know 
Feeling nervous, anxious, 
or on edge 
0 
1 
2 
3 
98 
Not being able to stop or 
control worrying 
0 
1 
2 
3 
98 
Feeling down, depressed, 
or hopeless 
0 
1 
2 
3 
98 
Little interest or pleasure 
in doing things 
0 
1 
2 
3 
98 
SEXUAL BEHAVIORS AND SEXUAL HISTORY 
Contact during sex is an important way in which some women get abnormalities on the cervix and 
anus. We need your help in understanding how women's behavior can affect their health. For this 
reason, it is very important for you to answer some questions about your personal sexual behavior. 
Each question will specify the type of sex to which we refer. Please consider any sexual 
experiences, even sex that was upsetting or involuntary such as rape. 
We assure you that your answers will be kept confidential. By providing this information, you will 
help us a great deal with this study. 
Please listen to each question carefully and answer as honestly as possible, even if you only had 
that type of sexual experience one time.  
8. Have you experienced sexual assault in the past 6 months? 
Response 
Code 
Yes 
1 
No 
2 
I don’t know 
98 
Decline to answer 
99 
Sex with Men 
The next questions refer only to vaginal sex with men. This is when a man puts his penis, fingers 
or a sex toy/object in a woman’s vagina. 
9. Have you had vaginal sex with a man in the past 6 months? 
No  
(skip to question 12) 
Yes 
Decline to answer 
(skip to question 12) 
0 
1 
99 
 

 
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10. How many men have you had vaginal sex with in the past 6 months? 
None 
1 
2-5 
6-10 
More than 
10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
11. How often were condoms used to cover the man’s penis, sex toy or object when you had vaginal 
sex with a man in the past 6 months? 
Never 
Rarely 
Sometime
s but less 
than half 
About 
half the 
time 
More 
than half 
the time 
Every 
time 
Unsure Decline to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 
Now I am going to ask you questions about anal sex with a man. This is when a man puts his penis, 
finger, sex toy or object in your anus. 
12. Have you had anal sex with a man in the past 6 months?  
No  
(skip to question 17) 
Yes 
Decline to answer 
(skip to question 17) 
0 
1 
99 
13. When was the last time a man put his penis in your anus? 
Within the 
past week 
Within the 
past month 
Within the 
past 6 
months 
Unsure 
Decline to 
answer 
1 
2 
3 
98 
99 
14. How many men have you had anal sex with in the past 6 months? 
None 
1 
2-5 
6-10 
More than 
10 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
4 
98 
99 
15. How often did you have anal sex with a man in the past 6 months? 
Never 
Less than 1 
time/month 
1-3 
times/ 
month 
Once/ 
week 
2-6 
times/ 
week 
Daily 
Unsure Decline to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 
16. How often was a condom used to cover the man’s penis, finger, sex toy or object when you had 
anal sex with a man in the past 6 months? 

 
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Never 
Rarely 
Sometime
s but less 
than half 
About 
half the 
time 
More 
than half 
the time 
Every 
time 
Unsure Decline to 
answer 
0 
1 
2 
3 
4 
5 
98 
99 
SEXUALLY TRANSMITTED INFECTIONS  
The following questions ask about infections and diseases that are sexually transmitted. Once 
again, I assure you that your answers will be kept confidential. 
Please let us know if, in the past 6 months, you have been diagnosed with or treated for any of the 
infections we ask about now. 
17. Have you had anal warts in the past 6 months? These are warts inside or around your anus. 
No 
Yes, in the 
past 6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
18. Have you had warts inside your vagina, on the vulva, or in both places in the past 6 months?  
No 
Inside 
Outside 
Both 
Unsure 
Decline to 
answer 
0 
1 
2 
3 
98 
99 
19. Have you had herpes around the vagina or anus in the past 6 months? These are painful blistering 
sores around your private parts. 
No 
Yes, in the 
past 6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
20. Have you had Chlamydia in the past 6 months? This is an infection transmitted during sexual 
contact. 
No 
Yes, in the 
past 6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
21. Have you had Gonorrhea (“clap”) in the past 6 months? This is an infection transmitted during 
sexual contact. 
No 
Yes, in the 
past 6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
 
 
 

 
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22. Have you had pelvic inflammatory disease (PID) or infection of your fallopian tubes or 
ovaries in the past 6 months? 
No 
Yes in the past 
6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
23. Have you had syphilis in the past 6 months? This is an infection transmitted during sexual 
contact. (The treatment is weekly painful penicillin shots.) 
No 
Yes in the past 
6 months 
Unsure/ 
Don’t know 
Decline to 
answer 
0 
1 
98 
99 
PRE-PROCEDURE EXPLANATION AND QUESTIONS [Acceptability] 
In addition to the previous questions, you have consented to have some procedures done today for 
this study. These procedures are an anal Pap smear, high resolution anoscopy and a biopsy of any 
abnormal tissue or area that is seen. 
Please tell me if you have any of the following concerns about having the following 
examinations or procedures. For each of these statements, please tell me whether you agree or 
disagree. Then you will be asked if you slightly or strongly agree/disagree with the statement. 
24. ANAL PAP SMEAR 
[OPTIONAL EXPLANATION: An anal Pap smear will be taken. This is like a cervical Pap smear. 
A Q-tip type swab will be inserted into the anus by the doctor or nurse practitioner to obtain cells 
that will be sent to the laboratory to check for abnormalities.] 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I 
am 
concerned 
about pain. 
1 
2 
3 
4 
5 
99 
I feel the exam will 
be uncomfortable. 
1 
2 
3 
4 
5 
99 
I feel at ease. 
1 
2 
3 
4 
5 
99 
I am prepared to 
have the procedure. 
1 
2 
3 
4 
5 
99 

 
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25. ONLY FOR VISITS 3 AND 5 
HIGH RESOLUTION ANOSCOPY  
[OPTIONAL EXPLANATION: High resolution anoscopy is done with use of a plastic tube 
instrument inserted in the anus to look at the tissue under a special light to see if there are warts 
or other abnormalities in the anal area. Vinegar is used to make any abnormal areas show up 
better under the light.  
Any abnormalities seen will be biopsied, or removed, with a small cutting instrument (after 
more numbing medication is injected) to send to the laboratory for special analysis.] 
Statement 
Strongly 
disagree 
Slightly 
disagree 
Neutral 
Slightly 
agree 
Strongly 
agree 
Decline to 
answer 
I 
am 
concerned 
about pain. 
1 
2 
3 
4 
5 
99 
I feel the exam will 
be uncomfortable. 
1 
2 
3 
4 
5 
99 
I feel at ease. 
1 
2 
3 
4 
5 
99 
I am prepared to 
have the procedure. 
1 
2 
3 
4 
5 
99 
26. Which of the following examinations or procedures concerns you the very most today? (Choose 
one) 
FOR VISITS 3 AND 5 
Code 
Procedure 
0 
No concern 
1 
Anal Pap smear 
2 
High resolution anoscopy 
3 
Biopsy 
99 
Decline to answer 
FOR VISITS 2 AND 4 
Code 
Procedure 
0 
No concern 
1 
Anal Pap smear 
99 
Decline to answer 
 
 

 
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HEALTH BEHAVIOR QUESTIONS 
Now I am going to ask you a few questions about yourself.  
[from ACTG self report, questions E, H, QL0742(A5257)/ 12-31-08] 
27. Are you on HIV medication(s)? 
No  
(skip to question 29) 
Yes 
Unsure/ 
Don’t know 
0 
1 
98 
28. Rate your ability to take all of your HIV medications as specifically prescribed. 
Very 
poor 
Poor 
Fair 
Good 
Very 
good 
Excellent 
N/A 
Unsure/ 
Don’t 
know 
Decline to 
answer 
1 
2 
3 
4 
5 
6 
97 
98 
99 
SMOKING QUESTIONS 
29. Have you smoked cigarettes in the past 6 months? 
No 
(skip to question 31) 
Yes 
0 
1 
AMC Smoking 
30. On average over the past 6 months, how many cigarettes have you smoked per day? (1 pack 
equals 20 cigarettes) 
______________________ (number of cigarettes) 
 
 

 
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COST/TRANSPORTATION QUESTIONS  
31. Which one best describes your hourly wage or annual income? 
Hourly Wage 
Annual Income 
$0.00 - $4.99 
$0.00 - $9,999 
$5.00 - $7.25 
$10,000 - $14,999 
$7.26 - $9.99  
$15,000 - $19,999 
$10.00 - $14.99 
$20,000 - $29,999 
$15.00 - $19.99 
$30,000 - $39,999 
$20.00 - $24.99 
$40,000 - $49,999 
$25.00 - $29.99 
$50,000 - $59,999 
$30.00 - $34.99 
$60,000 - $69,999 
$35.00 - $39.99 
$70,000 - $79,999 
$40.00 - $49.99 
$80,000 - $99,999 
More than $50.00/hour 
More than $100,000/year 
32. Did you miss work today for this visit? 
No 
Yes 
0 
1 
33. How did you get to the clinic today?  
Response 
Code 
Drive yourself 
1 
Get a ride from someone else in a personal vehicle 
2 
Take public transportation such as the metro bus or metro rail 
3 
Take a taxi 
4 
Walk or ride bike, or 
5 
Get there some other way (SPECIFY) ____________ 
6 
Decline to answer 
99 
34. If you took private/public transportation, what was the fare? 
$__________________ 

 
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35. How much time (including travelling time) will you miss from your usual activities because of 
this appointment? 
Response 
Code 
Less than 15 minutes 
1 
15 to 30 Minutes  
2 
31 Minutes to 60 Minutes (1 Hour) 
3 
61 Minutes to 90 Minutes  
4 
91 Minutes to 120 Minutes (2 Hours) 
5 
120 Minutes to 180 Minutes (2 to 3 Hours) 
6 
180 Minutes to 240 Minutes (3 to 4 Hours) 
7 
240 Minutes to 300 Minutes (4 to 5 Hours) 
8 
300 Minutes to 360 Minutes (5 to 6 Hours) 
9 
More than 360 Minutes (More than 6 Hours) 
10 
36. How far did you travel for this appointment? 
__________miles 
37. If you drove, how much do you expect to pay for the parking? $_________________ 
NA 
99 
38. If you are accompanied to your appointment by someone who missed work, what is the gender 
and age of this person? 
Accompanied 
Not 
accompanied 
Male 
Female 
Age 
0 
1 
2 
 
39. Did you have to get a caretaker today to attend to your children and/or an adult person living in 
your household in order to come to your appointment? 
No 
(Questionnaire complete) 
Yes 
0 
1 
40. How much do you expect to pay the caretaker for today? (If no payment, skip to next question)  
$____________ 
 
 

 
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41. Did the caretaker miss work in order to help you? 
No 
Yes 
0 
1 
42. What is the gender and age of the caretaker? 
Male 
Female 
Age 
1 
2