Increasing Cervical Cancer Screening Among Female Patients at Penn State Health St. Joe's Residency Clinic: Letter Notifying Them About Outdated Screen and Postcard With Self-sampling Option
Phase: NA
Conditions: Cervical Cancer Screening
Sponsor: Milton S. Hershey Medical Center

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St. Joe’s Invitation Effectiveness Study 
NCT04658888 
Last approval date 9/22/20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 2 of 34 (V.01/21/2019)  
                                                                                        
 
HRP-592 - Protocol for Human Subject  
Research with Use of Test Article(s) 
 
Protocol Title: 
Provide the full title of the study as listed in item 1 on the “Basic Information” page in CATS IRB (http://irb.psu.edu).  
Increasing cancer screening among female patients at PHS St. Joe’s residency clinic: Letter notifying them about 
outdated screen and postcard with self-sampling option 
 
Principal Investigator: 
Name: Christina Scartozzi, DO 
Department: Family & Community Medicine 
Telephone: 610-208-4610 
E-mail Address: craguckas@pennstatehealth.psu.edu 
 
Version Date: 
Provide the date of this submission. This date must be updated each time the submission is provided to the IRB office 
with revisions.  DO NOT revise the version date in the footer of this document.  
March 18, 2020September 22, 2020 
 
Clinicaltrials.gov Registration #: 
Provide the registration number for this study, if applicable. See “HRP-103- Investigator Manual, When do I have to 
register my project at ClinicalTrials.gov?” for more information.  
NCT04658888 
Important Instructions for Using This Protocol Template: 
This template is provided to help investigators prepare a protocol that includes the necessary information needed by the 
IRB to determine whether a study meets all applicable criteria for approval. 
 
1. 
GENERAL INSTRUCTIONS:   
• 
Prior to completing this protocol, ensure that you are using the most recent version by verifying the 
protocol template version date in the footer of this document with the current version provided in the 
CATS IRB Library. 
• 
Do not change the protocol template version date located in the footer of this document. 
• 
Some of the items may not be applicable to all types of research.  If an item is not applicable, please 
indicate as such or skip question(s) if indicated in any of the instructional text.  
• 
GRAY INSTRUCTIONAL BOXES:  
o Type your protocol responses below the gray instructional boxes of guidance language.  If the 
section or item is not applicable, indicate not applicable. 
o Penn State College of Medicine/Penn State Health researchers: Delete the instructional boxes 
from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).   
o Penn State researchers at all other campuses: Do NOT delete the instructional boxes from the 
final version of the protocol. 
• 
Add the completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic 
Information” page.   
2. 
CATS IRB LIBRARY:  
• 
Documents referenced in this protocol template (e.g. SOP’s, Worksheets, Checklists, and Templates) can be 
accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 

Page 3 of 34 (V.01/21/2019)  
 
3. 
PROTOCOL REVISIONS:  
• 
When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in 
the Study Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track 
changes.  
• 
Update the Version Date on page 1 each time revisions are made. 
 
 
If you need help… 
University Park and other campuses: 
Office for Research Protections Human Research 
Protection Program 
The 330 Building, Suite 205 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
College of Medicine and Penn State Health: 
Human Subjects Protection Office 
90 Hope Drive, Mail Code A115, P.O. Box 855 
Hershey, PA 17033 
(Physical Office Location: Academic Support Building 
Room 1140) 
Phone: 717-531-5687 
Email: irb-hspo@psu.edu   
 
 
 
 

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Table of Contents 
1.0 
Objectives 
2.0 
Background 
3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7.0 
Study Design and Procedures 
8.0 
Subject Numbers and Statistical Plan 
9.0 
Data and Safety Monitoring Plan 
10.0 
Risks 
11.0 
Potential Benefits to Subjects and Others 
12.0 
Sharing Results with Subjects 
13.0 
Subject Payment and/or Travel Reimbursements 
14.0 
Economic Burden to Subjects 
15.0 
Resources Available 
16.0 
Other Approvals 
17.0 
Multi-Site Study 
18.0 
Adverse Event Reporting 
19.0 
Study Monitoring, Auditing and Inspecting 
20.0 
Future Undetermined Research: Data and Specimen Banking 
21.0 
References 
22.0 
Confidentiality, Privacy and Data Management 
 
 
 

Page 5 of 34 (V.01/21/2019)  
1.0 
Objectives 
 
1.1 
Study Objectives 
Describe the purpose, specific aims or objectives.  State the hypotheses to be tested. 
 
The objective of this study is to evaluate the effectiveness of offering self-sampling for high-risk human 
papillomavirus (HPV) testing in increasing participation in cervical cancer screening. 
 
Specifically, we will determine if women who are out-of-date for cervical cancer screening will be more 
likely to seek screening if offered the option to complete a self-sampled HPV test compared to standard 
of care. Eligible patients at Penn State Health St. Joseph (seen through Family and Community Medicine 
and through Women’s Health) who are out-of-date with cervical cancer screening will be randomized to 
either a control arm or an intervention arm (2:1). Women in the control arm will receive a letter 
notifying them that they need to be screened and they should contact their primary care provider, 
according to standard clinical procedures (standard of care). Women in the experimental arm will 
receive (1) a slightly modified version of this letter informing them of a self-sampling option and (2) a 
pre-addressed post card to return to the study team if interested in self-sampling. Women who return 
the post card will then receive, via mail, a self-sampling kit to obtain a cervical sample for an HPV test. 
 
For both arms, women whose cervical cancer screening test (collected by a provider or by the 
participant herself) indicate the presence of high-risk HPV will be directed to follow-up procedures 
following standard clinical practice. 
 
Hypothesis: Women notified of a need for cervical cancer screening by letter who are offered self-
sampling for cervical cancer screening will have a higher rate of screening that women notified by letter 
alone. 
 
1.2 
Primary Study Endpoints 
State the primary endpoints to be measured in the study.   
 
Clinical trials typically have a primary objective or endpoint. Additional objectives and endpoints are 
secondary.  The endpoints (or outcomes), determined for each study subject, are the quantitative 
measurements required by the objectives.  Measuring the selected endpoints is the goal of a trial 
(examples: response rate and survival). 
 
The primary objective is to test the screening differences in control arm (i.e., receiving the standard 
reminder letter) versus the intervention arm (i.e., receiving a modified reminder letter plus postcard to 
request HPV self-sampling kit). The purpose is to assess the impact of mailing HPV home sampling kits to 
patients in need of cervical cancer screening on HPV screening rates.  
 
The primary end point of 1) Completion of cervical cancer screening 2) Use of home cervical cancer 
screening kit will be evaluated over a three month time period after reminder letters are mailed. 
 
1.3 
Secondary Study Endpoints 
State the secondary endpoints to be measured in the study. 
 
The secondary endpoint is overall cervical cancer screening of people mailed a letter. 
 

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2.0 
Background  
 
2.1 
Scientific Background and Gaps 
Describe the scientific background and gaps in current knowledge.  
 
For clinical research studies being conducted at Penn State Health/Penn State College of Medicine, and 
for other non-PSH locations as applicable, describe the treatment/procedure that is considered standard 
of care (i.e., indicate how patients would be treated in non-investigational setting); and if applicable, 
indicate if the treatment, drug, or device is available to patient without taking part in the study. 
 
The American Cancer Society estimates that 4,170 women in the United States (US) will die from cervical 
cancer in 2018. It is possible to prevent many of these deaths through screening (e.g., with the human 
papillomavirus [HPV] test for cervical cancer) and appropriate follow-up in women with positive 
screens.1 
 
The U.S. Preventive Services Task Force (USPSTF) recommends that women ages 30-65 receive cervical 
cancer screening through (a) Pap testing every 3 years; (b) high-risk HPV testing every 5 years; or (c) Pap 
and high-risk HPV testing every 5 years2. Other organizations, including the American College of 
Obstetrics and Gynecology and the American Cancer Society3, have different recommendations for the 
test modalities and intervals. Regardless of the specific measure of up-to-date with cervical cancer 
screening, rates of screening are suboptimal, and vulnerable subgroups (including women in rural areas, 
racial/ethnic minorities, women with low socioeconomic status, and women who are underinsured) are 
even less likely to be screened4. Most cases of cervical cancer are detected among women who are out-
of-date for screening5. 
 
An emerging area of evidence suggests that women can collect their own samples for high-risk HPV 
testing6,7. Offering self-sampling for HPV testing to women who are out-of-date for screening has been 
associated with up to 9 times higher rates of screening than a normal reminder letter8,9,10. This method 
of sample collection finds comparable clinical results as provider collection11, 12. In addition, this 
approach appears to be particularly effective among women who are out-of-date with screening13.  
 
Based on this information, self-sampling for HPV testing may be a viable option for cervical cancer 
screening, particularly among women who do not obtain regular screening in a clinical setting. However, 
all previous studies have been conducted in a highly-controlled, well-resourced research context. We 
propose a study using real-world procedures that could pragmatically be adopted in primary care clinics, 
i.e., evaluating a reminder letter with a post card option to request an HPV self-sampling kit. 
 
2.2 
Previous Data 
Describe any relevant preliminary data. 
 
Previous studies on HPV self-sampling have found this approach to be appropriate for providing 
preventive care to underserved communities. One recent study concluded that mailing self-sampling kits 
to home addresses could be a more effective alternative to reminder letters. 14 Other studies have 
demonstrated that HPV self-sampling tests are comparable to clinician-collected samples for HPV 
screening.15 
 
The study team has been involved in many studies on cancer prevention and control and primary care 
relevant to this proposal. Cancer prevention studies performed by the study team include ongoing 
studies on acceptability and accuracy of self-sampling. These studies emphasize the urgent need for 
interventions to improve cervical cancer screening behaviors in vulnerable communities.  
 

Page 7 of 34 (V.01/21/2019)  
2.3 
Study Rationale 
Provide the scientific rationale for the research. 
 
This pragmatic feasibility study will evaluate whether one method for offering self-sampling for HPV 
testing (i.e., with a post card to request a mailed kit) will increase cervical cancer screening rates. 
 
3.0 
Inclusion and Exclusion Criteria 
Create a numbered list below in sections 3.1 and 3.2 of criteria subjects must meet to be eligible for study 
enrollment (e.g., age, gender, diagnosis, etc.).  
 
Vulnerable Populations: 
 
Indicate specifically whether you will include any of the following vulnerable populations in this research. You 
MAY NOT include members of these populations as subjects in your research unless you indicate this in your 
inclusion criteria because specific regulations apply to studies that involve vulnerable populations.   
 
The checklists referenced below outline the determinations to be made by the IRB when reviewing research 
involving these populations. Review the checklists as these will help to inform your responses throughout the 
remainder of the protocol. 
 
• 
Children –Review “HRP-416- Checklist - Children” 
• 
Pregnant Women – Review “HRP-412- Checklist - Pregnant Women” 
• 
Cognitively Impaired Adults- Review “HRP-417- Checklist - Cognitively Impaired Adults”  
• 
Prisoners- Review “HRP-415- Checklist - Prisoners” 
• 
Neonates of uncertain viability or non-viable neonates- Review “HRP-413- Checklist - Non-Viable 
Neonates” or “HRP-414- Checklist - Neonates of Uncertain Viability” 
[Do not type here] 
 
3.1 
Inclusion Criteria 
Create a numbered list of the inclusion criteria that define who will be included in your final study 
sample (e.g., age, gender, condition, etc.)  
 
• 
Female patients at PSH St. Joe’s FCM residency clinic or women’s health clinic 
• 
30-65 years of age 
• 
Out-of-date for cervical cancer screening 
• 
Able to speak, read, and communicate well in English or Spanish 
• 
Not greater than average risk for cervical cancer 
 
3.2 
Exclusion Criteria 
Create a numbered list of the exclusion criteria that define who will be excluded in your study. 
 
• 
Pregnant 
• 
Incarcerated 
• 
Greater than average risk for cervical cancer16 
o Already diagnosed with high-grade precancerous cervical cancer or cervical lesions  
o Have  a compromised immune system 
o With in-utero exposure to diethylstilbestrol 

Page 8 of 34 (V.01/21/2019)  
• 
Unable to speak, read, and communicate well in English or Spanish 
• 
Unable or unwilling to give implied consent or otherwise complete study requirements 
 
3.3 
Early Withdrawal of Subjects 
3.3.1 
Criteria for removal from study 
Insert subject withdrawal criteria (e.g., safety reasons, failure of subject to adhere to protocol 
requirements, subject consent withdrawal, disease progression, etc.). 
 
There are no foreseeable reasons why a study subject might be removed by the investigators 
from the study. Subjects can voluntarily withdraw from the study at any time and for any 
reason. 
 
3.3.2 
Follow-up for withdrawn subjects 
Describe when and how to withdraw subjects from the study; the type and timing of the data to 
be collected for withdrawal of subjects; whether and how subjects are to be replaced; the 
follow-up for subjects withdrawn from investigational treatment. 
 
The withdrawal will be documented. Subjects who withdraw will be asked to describe why they 
are withdrawing so that we may better understand the study population. Withdrawn subjects 
will not be replaced but all data collected up until the point of withdraw will be included in data 
analysis.   
4.0 
Recruitment Methods 
▪ Upload recruitment materials for your study in CATS IRB (http://irb.psu.edu).  DO NOT include the actual 
recruitment wording in this protocol.   
▪ StudyFinder:  If StudyFinder (http://studyfinder.psu.edu) is to be used for recruitment purposes, separate 
recruitment documents do not need to be uploaded in CATS IRB. The necessary information will be captured 
from the StudyFinder page in your CATS IRB study.   
▪ Any eligibility screening questions (verbal/phone scripts, email, etc.) used when contacting potential 
participants must be uploaded to your study in CATS IRB (http://irb.psu.edu). 
 
We will use the EHR to identify women who are potentially-eligible for this study. We have developed a way 
to query to EHR to identify patients at PSH St. Joseph’s FCM or Women’s Health clinics, ages 30-65, who are 
out-of-date with cervical cancer screening, and who do not have documentation of disqualifying conditions. 
This query consists of a set of search parameters that will be entered into the EHR to identify participants 
who meet eligibility criteria.  
 
 
4.1 
Identification of subjects 
Describe the source of subjects and the methods that will be used to identify potential subjects (e.g., 
organizational listservs, established recruitment databases, subject pools, medical or school records, 
interactions during a clinic visit, etc.).   If not recruiting subjects directly (e.g., database query for eligible 
records or samples) state what will be queried, how and by whom. 
 
StudyFinder:   
o If you intend to use StudyFinder (http://studyfinder.psu.edu) for recruitment purposes, include this 
method in this section.  

Page 9 of 34 (V.01/21/2019)  
o Information provided in this protocol needs to be consistent with information provided on the 
StudyFinder page in your CATS IRB study. 
 
For Penn State Health submissions using Enterprise Information Management (EIM) for recruitment, and 
for non-Hershey locations as applicable, attach your EIM Design Specification form on in CATS IRB 
(http://irb.psu.edu). See “HRP-103- Investigator Manual, What is appropriate for study recruitment?” 
for additional information. DO NOT include the actual recruitment material or wording in this protocol. 
 
Participants will be recruited from St. Joe’s FCM or Women’s Health clinics that meet inclusion/exclusion 
criteria. As described in 4.1, we will identify these participants using the EHR. 
 
4.2 
Recruitment process 
Describe how potential subjects first learn about this research opportunity or indicate as not applicable 
if subjects will not be prospectively recruited to participant in the research.  Subject recruitment can 
involve various methods (e.g., approaching potential subjects in person, contacting potential subjects via 
email, letters, telephone, ResearchMatch, or advertising to a general public via flyers, websites, 
StudyFinder, newspaper, television, and radio etc.). DO NOT include the actual recruitment material or 
wording in this protocol. 
[Do not type here] 
 
4.2.1 
How potential subjects will be recruited. 
Potential participants will receive a letter notifying them that they are out-of-date with cervical 
cancer screening. Women in the control arm will receive a letter notifying them that they need 
to be screened and they should contact their primary care provider, according to standard 
clinical procedures (standard of care). Women in the experimental arm will receive (1) a slightly 
modified version of this letter informing them of a self-sampling option and (2) a pre-addressed 
post card to return to the study team if interested in self-sampling. Women who return the post 
card will then receive, via mail, a self-sampling kit to obtain a cervical sample for an HPV test. 
 
 
4.2.2 
Where potential subjects will be recruited. 
PSU St. Joseph’s FCM and Women’s Health clinics. 
4.2.3 
When potential subjects will be recruited. 
Participants will be continuously recruited from among potentially-eligible patients until the 
anticipated sample size has been met. Using a 2:1 randomization scheme, we will randomize 
807 participants to the control arm and 404 participants to the intervention arm. 
 
4.2.4 
Describe the eligibility screening process and indicate whether the screening process will 
occur before or after obtaining informed consent. Screening begins when the investigator 
obtains information about or from a prospective participant in order to determine their 
eligibility.  In some studies, these procedures may not take place unless HIPAA Authorization 
is obtained OR a waiver of HIPAA Authorization when applicable for the screening procedures 
is approved by the IRB.  [For FDA regulated studies, consent for any screening activities would 
need to be obtained prior to screening unless specifically waived by the IRB.] 
We have developed a way to query the EHR to identify patients at PSH St. Joseph’s FCM or 
Women’s Health clinics, ages 30-65, who are out-of-date with cervical cancer screening, and 
who do not have documentation of disqualifying conditions. The screening process will take 
place prior to the informed consent process.  

Page 10 of 34 (V.01/21/2019)  
 
5.0 
Consent Process and Documentation  
Refer to the following materials: 
• 
The “HRP-090- SOP - Informed Consent Process for Research” outlines the process for obtaining informed 
consent.   
• 
The “HRP-091– SOP - Written Documentation of Consent” describes how the consent process will be 
documented. 
• 
The “HRP-314- Worksheet - Criteria for Approval” section 7 lists the required elements of consent. 
• 
The “HRP-312- Worksheet - Exemption Determination” includes information on requirements for the 
consent process for exempt research.  In addition the CATS IRB Library contains consent guidance and 
templates for exempt research. 
• 
The CATS IRB library contains various consent templates for expedited or full review research that are 
designed to include the required information. 
• 
Add the consent document(s) to your study in CATS IRB (http://irb.psu.edu). Links to Penn State’s consent 
templates are available in the same location where they are uploaded. DO NOT include the actual consent 
wording in this protocol. 
[Do not type here] 
 
5.1 
Consent Process: 
Check all applicable boxes below: 
 
 Informed consent will be sought and documented with a written consent form [Complete Sections 
5.2 and 5.6]  
 
 Implied or verbal consent will be obtained – subjects will not sign a consent form (waiver of 
written documentation of consent) [Complete Sections 5.2, 5.3 and 5.6]  
 
  Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception). [Complete section 5.2, 5.4 and 5.6]  
 
 Informed consent will not be obtained – request to completely waive the informed consent 
requirement. [Complete Section 5.5] 
 
 
  
 
 
5.2 
Obtaining Informed Consent  
5.2.1 
Timing and Location of Consent  
Describe where and when the consent process will take place. 
 
Participants in the intervention arm will receive the HRP-586 along with the self-sampling kit in 
the mail.  
5.2.2 
Coercion or Undue Influence during Consent  
Describe the steps that will be taken to minimize the possibility of coercion or undue influence 
in the consent process. 
 

Page 11 of 34 (V.01/21/2019)  
During the screening phone call the study team member will stress that participation in this 
study is entirely voluntary.   
 
5.3 
Waiver of Written Documentation of Consent  
Review “HRP – 411 – Checklist – Waiver of Written Documentation of Consent.”  
 
 
 
5.3.1 
Indicate which of the following conditions applies to this research: 
  The research presents no more that minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
OR 
  The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 
will be asked whether the subject wants documentation linking the subject with the research, 
and the subject’s wishes will govern. (Note: This condition is not applicable for FDA-regulated 
research. If this category is chosen, include copies of a consent form and /or parental 
permission form for participants who want written documentation linking them to the 
research.) 
OR 
  If the subjects or legally authorized representatives are members of a distinct cultural group 
or community in which signing forms is not the norm, that the research presents no more 
than minimal risk of harm to subjects and provided there is an appropriate alternative 
mechanism for documenting that informed consent was obtained.  (Note: This condition is not 
applicable for FDA-regulated research.)  
 
Describe the alternative mechanism for documenting that informed consent was obtained: 
 
Participants in the postcard to request HPV self-sampling kit arm of the study will consent the 
study by sending back their postcards indicating that they want an HPV self-sampling kit. 
5.3.2 
Indicate what materials, if any, will be used to inform potential subjects about the research 
(e.g., a letter accompanying a questionnaire, verbal script, implied consent form, or summary 
explanation of the research) 
 
 The HRP-586 will accompany the self-sampling kit along with instructions on how to use the kit. 
Contact information for a study team member will be included on the HRP-586 so that 
participants can ask questions.  
 
5.4 
Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception). 
Review “HRP-410-Checklist -Waiver or Alteration of Consent Process” to ensure that you have provided 
sufficient information.   
 
5.4.1 
Indicate the elements of informed consent to be omitted or altered 
 
Not applicable. 
 

Page 12 of 34 (V.01/21/2019)  
5.4.2 
Indicate why the research could not practicably be carried out without the omission or 
alteration of consent elements 
 
Not applicable. 
 
5.4.3 
Describe why the research involves no more than minimal risk to subjects. 
 
Not applicable. 
 
 
5.4.4 
Describe why the alteration/omission will not adversely affect the rights and welfare of 
subjects. 
 
Not applicable. 
 
5.4.5 
If the research involves using identifiable private information or identifiable biospecimens, 
describe why the research could not be practicably be carried out without using such 
information or biospecimens in an identifiable format. 
 
Not applicable. 
 
5.4.6 
Debriefing  
Explain whether and how subjects will be debriefed after participation in the study. If subjects 
will not be debriefed, provide a justification for not doing so.  Add any debriefing materials to 
the study in CATS IRB. 
 
Not applicable. 
 
 
5.5 
Informed consent will not be obtained – request to completely waive the informed consent 
requirement 
Review “HRP-410-Checklist -Waiver or Alteration of Consent Process” to ensure that you have provided 
sufficient information. 
 
5.5.1 
Indicate why the research could not practicably be carried out without the waiver of consent 
 
Currently, patients do not need to provide informed consent to receive reminders to obtain 
guideline-recommended clinical procedures. Requiring participants to provide consent would 
critically reduce the sample size. More importantly, requiring potential participants to consent 
to receive information about cervical cancer screening could give them the impression that 
screening is somehow “new” or “experimental,” which could lead to patients who are out-of-
date with cervical cancer screening to avoid scheduling a screening. 
5.5.2 
Describe why the research involves no more than minimal risk to subjects. 
 

Page 13 of 34 (V.01/21/2019)  
Participants will receive a letter directing them to receive a guideline-recommended procedure 
that is considered standard of care. These procedures do not post more than minimal risks to 
subjects. 
 
5.5.3 
Describe why the alteration/omission will not adversely affect the rights and welfare of 
subjects. 
 
The rights and welfare of subjects will be maintained because they will still have the option of 
determining whether or not they want to schedule a cervical cancer screening. 
 
5.5.4 
If the research involves using identifiable private information or identifiable biospecimens, 
describe why the research could not be practicably be carried out without using such 
information or biospecimens in an identifiable format. 
 
Our outcomes analysis will assess (1) participation in cervical cancer screening during the follow-
up period (yes or no), and (2) whether any follow-up procedures were indicated for that patient. 
The follow up period will consist of three months after the mailing. We will assess differences in 
these outcomes for participants who receive the standard of care letter versus a modified letter 
with an option for HPV self-sampling. If we did not use identifiable health information, we would 
not be able to link the letter type to clinical outcomes.  
 
5.5.5 
Additional pertinent information after participation 
Explain if subjects will be provided with additional pertinent information after participation. If 
not applicable, indicate “not applicable.”    
 
Not Applicable. 
 
 
 
5.6 
Consent – Other Considerations  
 
5.6.1 
Non-English-Speaking Subjects 
Indicate what language(s) other than English are understood by prospective subjects or 
representatives. 
 
If subjects who do not speak English will be enrolled, describe the process to ensure that the 
oral and written information provided to those subjects will be in that language. Indicate the 
language that will be used by those obtaining consent. 
 
Indicate whether the consent process will be documented in writing with the long form of the 
consent documentation or with the short form of the consent documentation.  Review “HRP-
091 –SOP- Written Documentation of Consent” and “HRP-103 -Investigator Manual” to ensure 
that you have provided sufficient information.  
 
All participants will receive all materials in both English and Spanish. 
 
5.6.2 
Cognitively Impaired Adults 
Refer “HRP-417 -CHECKLIST- Cognitively Impaired Adults” for information about research 
involving cognitively impaired adults as subjects.  

Page 14 of 34 (V.01/21/2019)  
 
5.6.2.1 Capability of Providing Consent 
Describe the process to determine whether an individual is capable of consent. 
 
Not Applicable. 
 
5.6.2.2 Adults Unable to Consent 
Describe whether and how informed consent will be obtained from the legally 
authorized representative.  Describe who will be allowed to provide informed 
consent. Describe the process used to determine these individual’s authority to 
consent to research. 
 
For research conducted in the state of Pennsylvania, review “HRP-013 -SOP- Legally 
Authorized Representatives, Children and Guardians” to be aware of which 
individuals in the state of Pennsylvania meet the definition of “legally authorized 
representative.” 
 
For research conducted outside of the state of Pennsylvania, provide information 
that describes which individuals are authorized under applicable law to consent on 
behalf of a prospective subject to their participation in the procedure(s) involved in 
this research.  One method of obtaining this information is to have a legal counsel or 
authority review your protocol along with the definition of “children” in “HRP-013 -
SOP- Legally Authorized Representatives, Children, and Guardians.” 
 
Not Applicable. 
 
5.6.2.3 Assent of Adults Unable to Consent 
Describe the process for assent of the subjects.  Indicate whether assent will be 
required of all, some or none of the subjects.  If some, indicate which subjects will 
be required to assent and which will not.  
 
If assent will not be obtained from some or all subjects, provide an explanation of 
why not. 
 
Describe whether assent of the subjects will be documented and the process to 
document assent.  The IRB allows the person obtaining assent to document assent 
on the consent document and does not routinely require assent documents and 
does not routinely require subjects to sign assent documents. 
 
Not Applicable. 
 
5.6.3 
Subjects who are not yet adults (infants, children, teenagers)  
 
5.6.3.1 Parental Permission 
Describe whether and how parental permission will be obtained. If permission will 
be obtained from individuals other than parents, describe who will be allowed to 
provide permission.  Describe the process used to determine these individual’s 
authority to consent to each child’s general medical care. 
 

Page 15 of 34 (V.01/21/2019)  
For research conducted in the state of Pennsylvania, review “HRP-013-SOP- Legally 
Authorized Representatives, Children and Guardians” to be aware of which 
individuals in the state of Pennsylvania meet the definition of “children.”  
 
For research conducted outside of the state of Pennsylvania, provide information 
that describes which persons have not attained the legal age for consent to 
treatments or procedures involved in the research, under the applicable law of the 
jurisdiction in which research will be conducted.  One method of obtaining this 
information is to have a legal counsel or authority review your protocol along with 
the definition of “children” in “HRP-013-SOP- Legally Authorized Representatives, 
Children, and Guardians.” 
 
Not Applicable. 
 
5.6.3.2 Assent of subjects who are not yet adults 
Indicate whether assent will be obtained from all, some, or none of the children. If 
assent will be obtained from some children, indicate which children will be required 
to assent. When assent of children is obtained describe whether and how it will be 
documented. 
 
Not Applicable. 
 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
This section is about the access, use or disclosure of Protected Health Information (PHI). PHI is individually 
identifiable health information (i.e., health information containing one or more 18 identifiers) that is transmitted 
or maintained in any form or medium by a Covered Entity or its Business Associate. A Covered Entity is a health 
plan, a health care clearinghouse or health care provider who transmits health information in electronic form.  
See “HRP-103 -Investigator Manual” for a list of the 18 identifiers.   
 
If requesting a waiver/alteration of HIPAA authorization, complete sections 6.2 and 6.3 in addition to section 
6.1. The Privacy Rule permits waivers (or alterations) of authorization if the research meets certain conditions. 
Include only information that will be accessed with the waiver/alteration.  
[Do not type here] 
 
6.1 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
  
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable] 
 
 
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
 
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
 
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3] 
 

Page 16 of 34 (V.01/21/2019)  
 
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3] 
 
6.2 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1 
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
6.2.1.1 
Plan to protect PHI from improper use or disclosure 
Include the following statement as written – DO NOT ALTER OR DELETE 
unless this section is not applicable because the research does not involve a 
waiver of authorization. If the section is not applicable, remove the 
statement and indicate as not applicable.  
 
See the Research Data Plan Review Form. 
 
6.2.1.2 
Plan to destroy identifiers or a justification for retaining identifiers  
Describe the plan to destroy the identifiers at the earliest opportunity 
consistent with the conduct of the research. Include when and how 
identifiers will be destroyed. If identifiers will be retained, provide the legal, 
health or research justification for retaining the identifiers. 
 
Identifying information will be destroyed after data collection and cleaning is 
complete. 
 
6.2.2 
Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
Provide an explanation for why the research could not practicably be conducted without access 
to and use of PHI. 
 
Access to PHI is required to identify women who are within the specified age range (30-65 
years); out of date with cervical cancer screening; and don’t have any of the disqualifying 
conditions. 
 
Participants who request and return a self-sampling kit are providing their implied consent to 
collect their research information. Participants who do not request the self-sampling kit are 
receiving standard  
 
 
6.2.3 
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
Provide an explanation for why the research could not practicably be conducted without the 
waiver or alternation of authorization. 
 
Obtaining informed consent from all participants before accessing their PHI to determine 
screening status would be infeasible due to the large number of patients who meet inclusion 
criteria. Receiving a reminder letter about cervical cancer screening is also standard of care for 
those who are out-of-date, so there would be no reason to consent these patients prior to 
sending the letter.  
 

Page 17 of 34 (V.01/21/2019)  
6.3 
Waiver or alteration of authorization statements of agreement 
 
By submitting this study for review with a waiver of authorization, you agree to the following statement – 
DO NOT ALTER OR DELETE unless this section is not applicable because the research does not involve a 
waiver or alteration of authorization. If the section is not applicable, remove the statement and indicate 
as not applicable. 
 
Not Applicable. 
 
 
7.0 
Study Design and Procedures 
Data collection materials that will be seen or used by subjects in your study must be uploaded to CATS IRB 
(http://irb.psu.edu).   DO NOT include any actual data collection materials in this protocol (e.g., actual survey or 
interview questions) 
 
[Do not type here] 
 
7.1 
Study Design 
Describe and explain the study design. 
 
Invitation letters will be sent out by a study team member to Penn State Health St. Joseph patients who 
meet the inclusion/exclusion criteria. Participants will receive either (1) a standardized letter informing 
them that they are out-of-date and should schedule an appointment for their cervical cancer screening 
(control arm) or (2) a modified version of this letter, plus a pre-addressed postcard to request an HPV 
self-sampling kit (intervention arm). Kits will be mailed out to those that indicate they want to receive 
one along with the HRP-586 consent form. Participants will mail self-collected cervical samples to the 
PSH Hershey lab for processing. A sample is stable for up to 6 months at room temperature: 
https://www.sciencedirect.com/science/article/pii/S2405852118300089. If we receive test kits returned 
after that timeframe, we will discard the sample and exclude those results. If negative result, patient will 
be contacted by a study physician with results. If positive result for low-risk HPV, patient will be 
contacted by a study physician to schedule a Pap test. If positive result for high-risk HPV, patient will be 
contacted by a study physician to schedule a colposcopy. Scheduling a Pap or Colposcopy test is 
standard of care for a low-risk or high-risk HPV result, respectively. The study team will monitor receipt 
of cervical cancer screening across the two arms. 
 
7.2 
Study Procedures 
Provide a step by step description of all research procedures being conducted (broken down by visit, if 
applicable) including such information as below (where and when applicable); describe the following: 
• 
HOW: (e.g., data collection via interviews, focus groups, forms such as surveys and questionnaires, 
medical/school records, audio/video/digital recordings, photographs, EKG procedures, MRI, mobile 
devices such as electronic tablets/cell phones, observations, collection of specimens, experimental 
drug/device testing, manipulation of behavior/use of deception, computer games, etc.) 
• 
WHERE: (e.g., classrooms, labs, internet/online, places of business, medical settings, public spaces, 
etc.) 
 
 [Type protocol text here] 
 
7.2.1 
Prior to mailing 
Provide a description of what procedures will be performed on visit 1 or day 1 or pre-test in 
order of how these will be done.  If your study only involves one session or visit, use this section 
only and indicate 7.2.2 as not applicable.  

Page 18 of 34 (V.01/21/2019)  
 
We have developed a way to query to EHR to identify patients at PSH St. Joseph’s FCM or 
Women’s Health clinics, ages 30-65, who are out-of-date with cervical cancer screening, and 
who do not have documentation of disqualifying conditions. After generating this list, we will 
use REDCap to randomize participants to the control arm or intervention arm (2:1). The study 
team will then prepare mailings of letters (control arm) or letters with postcards (intervention 
arm) to send to participants. 
 
 
7.2.2 
Mailings 
Provide a description of what procedures will be performed on visit 2 or day 2 or post-test in 
order of how these will be done.  If your study involves more than two sessions or visits 
replicate this section for each additional session or visit (e.g., 7.2.3, 7.2.4, etc.).  
 
Once participants are randomized, they will then be sent a reminder letter in English and 
Spanish inviting them to schedule a screening. Participants in the intervention arm will receive a 
modified version of this letter, as well as a pre-addressed, pre-stamped postcard to request an 
HPV self-sampling kit.  
 
7.3 
Duration of Participation 
Describe how long subjects will be involved in this research study.  Include the number of sessions and 
the duration of each session - consider the total number of minutes, hours, days, months, years, etc.   
 
The duration of the participation will be up to three months for active monitoring. 
 
7.4 
Test Article(s) (Study Drug(s) and/or Study Device(s)) 
 
7.4.1 
Description 
Provide a brief description of all test articles (drugs (including any foods and dietary 
supplements), devices and/or biologics used in the research including the purpose of their use 
and their approval status with the Food and Drug Administration (FDA). Include information 
about the form of the drug product (e.g., tablets, capsules, liquid). 
 
The Evalyn® Brush is a self-sampling kit that screens for HPV, a leading cause of cancer death 
among women. This tool has recently been FDA approved, but has not been incorporated into 
national clinical guidelines. This product is a small pink capped brush that can be used to take a 
sample of cervical cells.  
 
7.4.2 
Treatment Regimen 
Describe dose, route of administration and treatment duration. Include information about dose 
adjustments. 
 
Participants will take a sample of their cervix cells that amounts to a few millimeters of bio 
specimen. 
 
7.4.3 
Method for Assigning Subject to Treatment Groups 
Describe the randomization process and how the associated treatment assignment will be 
made. 

Page 19 of 34 (V.01/21/2019)  
 
Not applicable. 
 
7.4.4 
Subject Compliance Monitoring 
Insert the procedures for monitoring subject compliance. 
 
Subject compliance will be confirmed once their lab results are received from the Penn State 
Heath Clinical lab.  
 
7.4.5 
Blinding of the Test Article 
Describe how the test article is blinded. 
 
Not applicable. 
7.4.6 
Receiving, Storage, Dispensing and Return  
 
7.4.6.1 
Receipt of Test Article  
Describe how the test article will be obtained and from what source. 
Describe how the study test article will be packaged along with amounts 
(e.g., number of tablets/capsules or volume of liquid) and labeling. If drug 
kits are used, describe all the contents of the kit and associated labeling. 
 
1 HPV self-sampling kit will be sent to the Penn State Heath Clinical lab in a 
prepaid mailing. Inside the mailing will be the HPV self-sampling kit with 
the instructions and a Penn State Heath Clinical lab Pathology Services 
Special Account Requisition form. 
 
7.4.6.2 
Storage 
Describe the plans to store, handle the test article so they will be used only 
on subjects and only by authorized investigators. Describe storage 
temperature requirements and how temperature will be monitored and 
recorded. 
 
Before HPV self-sampling kits are sent to study participants, they will be 
stored in a locked cabinet in the Department of Family and Community 
Medicine offices at 134 Sipe Ave. Kits mailed to the lab will be disposed of 
after analysis.  
 
7.4.6.3 
Preparation and Dispensing 
Describe how the test article will be assigned to each subject and 
dispensed. Describe the steps necessary to prepare the test article. Include 
where the test article preparation will be done and by whom. Fully 
describe how the study treatment is to be administered and by whom. 
 
Before it is sent to the participant, the Penn State Heath Clinical lab 
Pathology Services Special Account Requisition document will be labeled 
with the participant’s ID #, date of birth, and sex. The Mailing will include 
the HPV self-sampling kit with the instructions, a summary explanation of 
research, Penn State Heath Clinical lab Pathology Services Special Account 

Page 20 of 34 (V.01/21/2019)  
Requisition form. Also, the package will include a prepaid and labeled 
mailing to send the kit and Pathology Services Special Account Requisition 
document to the Penn State Heath Clinical lab. Participants will need to 
include the date and time of sample collection on the Requisition form. 
 
7.4.6.4 
Return or Destruction of the Test Article 
Describe the procedures for final reconciliation of the test article supply at 
the end of the study and whether the test article is to be shipped back to a 
source or destroyed on site. 
 
HPV self-sampling kits will not be returned to participants. The samples will 
be analyzed and the kits will be destroyed by the Penn State Heath Clinical 
lab once analysis is complete. 
 
7.4.6.5 
Prior and Concomitant Therapy 
Describe what prior and/or concomitant medical therapy will be collected. 
Describe which concomitant medicines/therapies are permitted during the 
study. Describe which concomitant medicines are not permitted during the 
study. 
 
Not applicable. 
 
8.0 
Subject Numbers and Statistical Plan 
 
8.1 
Number of Subjects 
Indicate the maximum number of subjects to be accrued/enrolled. Distinguish between the number of 
subjects who are expected to be enrolled and screened, and the number of subjects needed to 
complete the research procedures if applicable (i.e., numbers of subjects excluding screen failures.) 
 
The study seeks to have 1,211 participants. There will be 807 participants randomized into the control 
arm and 404 into the intervention arm. 
 
8.2 
Sample size determination 
If applicable, provide a justification of the sample size outlined in section 8.1  to include reflections on, 
or calculations of, the power of the study. 
 
We assume a 15% response rate from the control group, i.e., in response to a standard reminder letter, 
for a final n=122.17 We further assume a 30% response rate for the intervention group, i.e., requesting 
an HPV self-sampling 18 kit, for a final n=122 for this group. In total, we expect at least 244 participants to 
respond to their reminders to receive cervical cancer screening. 
 
8.3 
Statistical methods 
Describe the statistical methods (or non-statistical methods of analysis) that will be employed. 
 
We will calculate the proportion of participants who obtain cervical cancer screening (in the Penn State 
Health St. Joseph’s FCM or Women’s Health clinics or with self-collected samples for HPV testing) by arm 
within three months of the initial mailing. We will use chi-squared tests to compare these proportions, 
using an alpha of .05 and a beta of 0.80.  
 

Page 21 of 34 (V.01/21/2019)  
9.0 
Data and Safety Monitoring Plan 
This section is required when research involves more than Minimal Risk to subjects as defined in “HRP-001 
SOP- Definitions.” 
 
Minimal Risk is defined as the probability and magnitude of harm or discomfort anticipated in the research that 
are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.  For research involving prisoners, Minimal Risk is the 
probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in 
the routine medical, dental, or psychological examination of healthy persons.  
 
Please complete the sections below if the research involves more than minimal risk to subjects, otherwise 
indicate each section as not applicable.  
[Do not type here] 
See the Research Data Plan Review Form 
 
9.1 
Periodic evaluation of data 
Describe the plan to periodically evaluate the data collected regarding both harms and benefits to 
determine whether subjects remain safe. 
 
Not applicable. 
 
9.2 
Data that are reviewed 
Describe the data that are reviewed, including safety data, untoward events, and efficacy data. 
 
Not applicable. 
 
9.3 
Method of collection of safety information 
Describe the method by which the safety information will be collected (e.g., with case report forms, at 
study visits, by telephone calls and with subjects). 
 
Not applicable. 
 
9.4 
Frequency of data collection 
Describe the frequency of data collection, including when safety data collection starts. 
 
Not applicable. 
 
9.5 
Individuals reviewing the data 
Identify the individuals who will review the data. The plan might include establishing a data and safety 
monitoring committee and a plan for reporting data monitoring committee findings to the IRB and the 
sponsor. 
 
Not applicable. 
 

Page 22 of 34 (V.01/21/2019)  
9.6 
Frequency of review of cumulative data 
Describe the frequency or periodicity of review of cumulative data. 
 
Not applicable. 
 
9.7 
Statistical tests 
Describe the statistical tests for analyzing the safety data to determine whether harms are occurring. 
 
Not applicable. 
 
9.8 
Suspension of research 
Describe any conditions that trigger an immediate suspension of research. 
 
Not applicable. 
 
10.0 Risks 
List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects related the 
subjects’ participation in the research. Include as may be useful for the IRB’s consideration, a description of the 
probability, magnitude, duration and reversibility of the risks. Consider all types of risk including physical, 
psychological, social, legal, and economic risks.  Note: Loss of confidentiality is a potential risk when conducting 
human subject research. 
• 
If applicable, indicate which procedures may have risks to the subjects that are currently unforeseeable. 
• 
If applicable, indicate which procedures may have risks to an embryo or fetus should the subject be or 
become pregnant. 
• 
If applicable, describe risks to others who are not subjects. 
 
Potential risks associated with these procedures are minimal. Loss of confidentiality is a risk of participation. 
Participant’s personal information will be stored in REDCap, which will be accessible only to study team 
members that need it.  
 
Participants in the intervention arm who complete cervical cancer screening using a self-collected HPV test only 
may not necessarily receive a Pap test. There may be concerns that these women will have a missed cancer 
diagnosis. However, a negative result on an HPV DNA test is better at predicting later disease than a negative 
result on a Pap test19. Based on the body of evidence, USPSTF has determined that HPV testing without cotesting 
with Pap is adequate as a primary cervical cancer screening approach2. 
 
There may be some risk involved with the self-sampling kit from the way it is used. Participants can suffer some 
internal injuries if they do not use the insertion tools properly. The likelihood of these injuries is minimal. 
 
11.0 Potential Benefits to Subjects and Others  
11.1 
Potential Benefits to Subjects 
Describe the potential benefits that individual subjects may experience from taking part in the research. 
If there is no direct benefit to subjects, indicate as such. Compensation is not considered a benefit. 
Compensation should be addressed in section 14.0. 
 

Page 23 of 34 (V.01/21/2019)  
The potential benefits to subjects could be the opportunity to get their cancer identified and treated if 
they decide to participate and take the recommendation to get cervical cancer screening. 
 
11.2 
Potential Benefits to Others 
Include benefits to society or others.  
 
In the long-term, this study may be a useful way of finding out how best to get under screened patients 
to receive regular cervical cancer screening and improve screening rates. 
 
12.0 Sharing Results with Subjects 
Describe whether results (study results or individual subject results, such as results of investigational diagnostic 
tests, genetic tests, or incidental findings) will be shared with subjects or others (e.g., the subject’s primary care 
physicians) and if so, describe how information will be shared.  
 
Not Applicable. 
 
13.0 Subject Payment and/or Travel Reimbursements 
Describe the amount, type (cash, check, gift card, other) and timing of any subject payment or travel 
reimbursement. If there is no subject payment or travel reimbursement, indicate as not applicable.  
 
Extra or Course Credit:  Describe the amount of credit and the available alternatives. Alternatives should be 
equal in time and effort to the amount of course or extra credit offered. It is not acceptable to indicate that the 
amount of credit is to be determined or at the discretion of the instructor of the course.  
 
Approved Subject Pool: Indicate which approved subject pool will be used; include in response below that 
course credit will be given and alternatives will be offered as per the approved subject pool procedures.  
 
None. 
 
14.0 Economic Burden to Subjects 
14.1 
Costs 
Describe any costs that subjects may be responsible for because of participation in the research. 
 
None. 
 
14.2 
Compensation for research-related injury 
If the research involves more than Minimal Risk to subjects, describe the available compensation in 
the event of research related injury. 
 
If there is no sponsor agreement that addresses compensation for medical care for research subjects 
with a research-related injury, include the following text as written - DO NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers.  

Page 24 of 34 (V.01/21/2019)  
 
For sponsored research studies with a research agreement with the sponsor that addresses 
compensation for medical care for research-related injuries, include the following text as written - DO 
NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Such charges may be paid by the study sponsor as 
outlined in the research agreement and explained in the consent form. 
 
Not Applicable. 
 
 
15.0 Resources Available  
 
15.1 
Facilities and locations 
Identify and describe the facilities, sites and locations where recruitment and study procedures will be 
performed.  
 
If research will be conducted outside the United States, describe site-specific regulations or customs 
affecting the research, and describe the process for obtaining local ethical review. Also, describe the 
principal investigator’s experience conducting research at these locations and familiarity with local 
culture. 
 
Participants will be recruited through collaboration with St. Joseph’s Family and Community Medicine 
and Women’s Health clinics. Participant will be identified through a previously-developed EHR data pull 
and recruited from their active patient files. 
 
15.2 
Feasibility of recruiting the required number of subjects 
Indicate the number of potential subjects to which the study team has access.  Indicate the percentage 
of those potential subjects needed for recruitment. 
 
St. Joseph’s Family and Community Medicine and Women’s Health clinics sees thousands of patients 
each year. The most recent EHR data pull indicated ~1500 women who met inclusion/exclusion criteria 
for this study. 
 
15.3 
PI Time devoted to conducting the research 
Describe how the PI will ensure that a sufficient amount of time will be devoted to conducting and 
completing the research. Please consider outside responsibilities as well as other on-going research for 
which the PI is responsible. 
 
The PI will utilize dedicated research time to conduct this research. 
 
15.4 
Availability of medical or psychological resources 
Describe the availability of medical or psychological resources that subjects might need as a result of 
their participation in the study, if applicable. 
 

Page 25 of 34 (V.01/21/2019)  
Not Applicable. 
 
15.5 
Process for informing Study Team 
Describe the training plans to ensure members of the research team are informed about the protocol 
and their duties, if applicable. 
 
The research team will meet regularly to discuss this study, its procedures, and any issues that may 
arise. 
 
16.0 Other Approvals 
16.1 
Other Approvals from External Entities 
Describe any approvals that will be obtained prior to commencing the research (e.g., from engaged 
cooperating institutions IRBs who are also reviewing the research and other required review 
committees, community leaders, schools, research locations where research is to be conducted by the 
Penn State investigator, funding agencies, etc.). 
 
This research study is unfunded. 
 
16.2 
Internal PSU Committee Approvals 
 
Check all that apply: 
  Anatomic Pathology – Penn State Health only – Research involves the collection of tissues or use of 
pathologic specimens. Upload a copy of “HRP-902 - Human Tissue For Research Form” in CATS IRB.  
 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
 
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA 
or gene therapy). 
 
  Clinical Laboratories – Penn State Health only – Collection, processing and/or storage of extra tubes 
of body fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids 
that had been collected for clinical purposes but are no longer needed for clinical use. Upload a copy 
of “HRP-901 - Human Body Fluids for Research Form” in CATS IRB.  
 
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of 
CRC services in any way. 
 
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
  Radiation Safety – Penn State Health only – Research involves research-related radiation 
procedures. All research involving radiation procedures (standard of care and/or research-related) 
must upload a copy of “HRP-903 - Radiation Review Form” in CATS IRB.  
 

Page 26 of 34 (V.01/21/2019)  
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE. 
 
  Scientific Review – Penn State Health only – All investigator-written research studies requiring 
review by the convened IRB must provide documentation of scientific review with the IRB 
submission. The scientific review requirement may be fulfilled by one of the following: (1) external 
peer-review process; (2) department/institute scientific review committee; or (3) scientific review by 
the Clinical Research Center Advisory committee.  NOTE: Review by the Penn State Health Cancer 
Institute (PSCI) Protocol Review Committee or the PSCI Disease Team is required if the study 
involves cancer prevention studies or cancer patients, records and/or tissues. For more information 
about this requirement see the IRB website. 
 
17.0 Multi-Site Study 
If this is a multi-site study (i.e., a study in which two or more institutions coordinate, with each institution 
completing all research activities outlined in a specific protocol) and the Penn State PI is the lead investigator, 
describe the processes to ensure communication among sites in the sections below. 
[Do not type here] 
 
17.1 
Other sites  
List the name and location of all other participating sites. Provide the name, qualifications and contact 
information for the principal investigator at each site and indicate which IRB will be reviewing the study 
at each site. 
 
 
 
 
Not Applicable. 
 
17.2 
Communication Plans 
Describe the plan for regular communication between the overall study director and the other sites to 
ensure that all sites have the most current version of the protocol, consent document, etc.  Describe the 
process to ensure all modifications have been communicated to sites. Describe the process to ensure 
that all required approvals have been obtained at each site (including approval by the site’s IRB of 
record).   Describe the process for communication of problems with the research, interim results and 
closure of the study. 
 
Not Applicable. 
 
17.3 
Data Submission and Security Plan 
Describe the process and schedule for data submission and provide the data security plan for data 
collected from other sites.  Describe the process to ensure all engaged participating sites will safeguard 
data as required by local information security policies. 
 
Not Applicable. 
 
17.4 
Subject Enrollment 
Describe the procedures for coordination of subject enrollment and randomization for the overall 
project. 
 
Not Applicable. 
 

Page 27 of 34 (V.01/21/2019)  
17.5 
Reporting of Adverse Events and New Information 
Describe how adverse events and other information will be reported from the clinical sites to the overall 
study director. Provide the timeframe for this reporting. 
 
Not Applicable. 
 
17.6 
Audit and Monitoring Plans 
Describe the process to ensure all local site investigators conduct the study appropriately. Describe any 
on-site auditing and monitoring plans for the study. 
 
Not Applicable. 
 
18.0 Adverse Event Reporting 
18.1 
Adverse Event Definitions 
 
For drug studies, incorporate the following definitions into the below responses, as written: 
Adverse event 
Any untoward medical occurrence associated with the use of the drug in 
humans, whether or not considered drug related 
Adverse reaction 
Any adverse event caused by a drug 
Suspected adverse 
reaction 
Any adverse event for which there is a reasonable possibility that the drug 
caused the adverse event.  Suspected adverse reaction implies a lesser degree 
of certainty about causality than “adverse reaction”. 
• 
Reasonable possibility.  For the purpose of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event. 
Serious adverse 
event or Serious 
suspected adverse 
reaction 
Serious adverse event or Serious suspected adverse reaction: An adverse event 
or suspected adverse reaction that in the view of either the investigator or 
sponsor, it results in any of the following outcomes: Death, a life-threatening 
adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption 
of the ability to conduct normal life functions, or a congenital anomaly/birth 
defect. Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based 
upon appropriate medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  
Life-threatening 
adverse event or 
life-threatening 
suspected adverse 
reaction 
An adverse event or suspected adverse reaction is considered “life-
threatening” if, in the view of either the Investigator (i.e., the study site 
principal investigator) or Sponsor, its occurrence places the patient or research 
subject at immediate risk of death.  It does not include an adverse event or 
suspected adverse reaction that had it occurred in a more severe form, might 
have caused death. 
Unexpected 
adverse event or 
Unexpected 
suspected adverse 
reaction.   
An adverse event or suspected adverse reaction is considered “unexpected” if 
it is not listed in the investigator brochure, general investigational plan, clinical 
protocol, or elsewhere in the current IND application; or is not listed at the 
specificity or severity that has been previously observed and/or specified. 
 
 
 
For device studies, incorporate the following definitions into the below responses, as written: 

Page 28 of 34 (V.01/21/2019)  
Unanticipated 
adverse device 
effect 
Any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or IDE application (including a supplementary plan 
or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
18.2 
Recording of Adverse Events 
Address the frequency and process for eliciting adverse event information from research subject, e.g., 
“Research subjects will be routinely questioned about adverse events at study visits.” 
 
In the response, incorporate the following as written: 
All adverse events (serious or non-serious) and abnormal test findings observed or reported to study 
team believed to be associated with the study drug(s) or device(s) will be followed until the event (or 
its sequelae) or the abnormal test finding resolves or stabilizes at a level acceptable to the 
investigator. 
 
An abnormal test finding will be classified as an adverse event if one or more of the following criteria 
are met: 
• 
The test finding is accompanied by clinical symptoms 
• 
The test finding necessitates additional diagnostic evaluation(s) or medical/surgical 
intervention; including significant additional concomitant drug treatment or other therapy 
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does 
not constitute an adverse event. 
• 
The test finding leads to a change in study drug dosing or discontinuation of subject 
participation in the clinical research study 
• 
The test finding is considered an adverse event by the investigator. 
 
All adverse events (serious or non-serious) and abnormal test findings observed or reported to study 
team believed to be associated with the study drug(s) or device(s) will be followed until the event (or its 
sequelae) or the abnormal test finding resolves or stabilizes at a level acceptable to the investigator. 
 
An abnormal test finding will be classified as an adverse event if one or more of the following criteria are 
met: 
• 
The test finding is accompanied by clinical symptoms 
• 
The test finding necessitates additional diagnostic evaluation(s) or medical/surgical intervention; 
including significant additional concomitant drug treatment or other therapy 
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does not 
constitute an adverse event. 
• 
The test finding leads to a change in study drug dosing or discontinuation of subject 
participation in the clinical research study 
• 
The test finding is considered an adverse event by the investigator. 
 
18.3 
Causality and Severity Assessments 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE:  
 
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event. 
 

Page 29 of 34 (V.01/21/2019)  
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history. 
 
18.4 
Reporting of Adverse Reactions and Unanticipated Problems to the FDA. 
 
18.4.1 Written IND/IDE Safety Reports 
For a drug study under an IND, incorporate the following from 21 CFR 312.32 as written – DO 
NOT ALTER OR DELETE:  
The Sponsor-Investigator will submit a written IND Safety Report (i.e., completed FDA Form 
3500A) to the responsible new drug review division of the FDA for any observed or volunteered 
adverse event that is determined to be a serious and unexpected, suspected adverse reaction.  
Each IND Safety Report will be prominently labeled, “IND Safety Report”, and a copy will be 
provided to all participating investigators (if applicable) and sub-investigators. 
 
Written IND Safety Reports will be submitted to the FDA as soon as possible and, in no event, 
later than 15 calendar days following the Sponsor-Investigator’s receipt of the respective 
adverse event information and determination that it meets the respective criteria for reporting. 
 
For each written IND Safety Report, the Sponsor-Investigator will identify all previously 
submitted IND Safety Reports that addressed a similar suspected adverse reaction experience 
and will provide an analysis of the significance of newly reported, suspected adverse reaction in 
light of the previous, similar report(s) or any other relevant information. 
 
Relevant follow-up information to an IND Safety Report will be submitted to the applicable 
review division of the FDA as soon as the information is available and will be identified as such 
(i.e., “Follow-up IND Safety Report”). 
 
If the results of the Sponsor-Investigator’s follow-up investigation show that an adverse event 
that was initially determined to not require a written IND Safety Report does, in fact, meet the 
requirements for reporting; the Sponsor-Investigator will submit a written IND Safety Report as 
soon as possible, but in no event later than 15 calendar days, after the determination was made. 
 
For a device study under an IDE, incorporate the following from 21 CFR 812.150 as written – 
DO NOT ALTER OR DELETE:  
The Sponsor-Investigator will submit a completed FDA Form 3500Ato the FDA’s Center for 
Devices and Radiological Health for any observed or volunteered adverse effect that is 
determined to be an unanticipated adverse device effect.  A copy of this completed form will be 
provided to all participating sub-investigators. 
 
The completed FDA Form 3500Awill be submitted to the FDA as soon as possible and, in no 
event, later than 10 working days after the Sponsor-Investigator first receives notice of the 
adverse effect. 
 
If the results of the Sponsor-Investigator’s follow-up evaluation show that an adverse effect that 
was initially determined to not constitute an unanticipated adverse device effect does, in fact, 
meet the requirements for reporting; the Sponsor-Investigator will submit a completed FDA 
Form 3500Aas soon as possible, but in no event later than 10 working days, after the 
determination was made. 
 

Page 30 of 34 (V.01/21/2019)  
For each submitted FDA Form 3500A, the Sponsor-Investigator will identify all previously 
submitted reports that that addressed a similar adverse effect experience and will provide an 
analysis of the significance of newly reported adverse effect in light of the previous, similar 
report(s).  
 
Subsequent to the initial submission of a completed FDA Form 3500A, the Sponsor-Investigator 
will submit additional information concerning the reported adverse effect as requested by the 
FDA. 
 
Not Applicable. 
 
18.4.2 Telephoned IND Safety Reports – Fatal or Life-threatening Suspected Adverse Reactions 
For a drug study under an IND, incorporate the following from 21 CFR 312.32 into the 
response, as written: 
In addition to the subsequent submission of a written IND Safety Report (i.e., completed FDA 
Form 3500A), the Sponsor-Investigator will notify the responsible review division of the FDA by 
telephone or facsimile transmission of any unexpected, fatal or life-threatening suspected 
adverse reaction.  
 
The telephone or facsimile transmission of applicable IND Safety Reports will be made as soon 
as possible but in no event later than 7 calendar days after the Sponsor-Investigator’s receipt of 
the respective adverse event information and determination that it meets the respective criteria 
for reporting. 
 
Not Applicable. 
 
18.5 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE:  
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
18.6 
Unblinding Procedures 
Describe the procedures for unblinding study therapy on a subject, including documentation of this in 
the subject’s source document. Include example(s) here why someone might unblind a study. In most 
cases, the unblinding will be part of managing a serious adverse reaction and will be reported with the 
serious adverse event. However, in cases where unblinding was not associated with a serious adverse 
event, such actions should be reported in a timely manner. 
 
Not Applicable. 
 
18.7 
Stopping Rules 
In studies with a primary safety endpoint or studies with high risk to study subjects, provide the rules 
that define the circumstances and procedures for interrupting or stopping the study. If an independent 
Data and Safety Monitoring (DSMB) or Committee (DSMC) is set up for the study, the same stopping 
rules should be incorporated into the safety analysis plan as well. 
 
Not Applicable. 

Page 31 of 34 (V.01/21/2019)  
 
19.0 Study Monitoring, Auditing and Inspecting 
 
19.1 
Study Monitoring Plan  
 
 
19.1.1 Quality Assurance and Quality Control 
Include this section if FDA regulations apply to this study (see “WORKSHEET: Drugs (HRP-306)” 
and “WORKSHEET: Devices (HRP-307)”. HRP-306 and HRP-307 can be accessed by clicking the 
Library link in CATS IRB (http://irb.psu.edu).  
 
Describe how you will ensure that this study is conducted and that the data are generated, 
documented (recorded) and reported in compliance with this protocol, with institutional and 
IRB policies, with Good Clinical Practice guidelines and any other applicable regulatory 
requirements. 
 
Indicate who is responsible for monitoring the conduct of the study and specify how often the 
study will be monitored.  
 
For single-site studies with low risk, it may be appropriate for the principal investigator to 
monitor the study. 
 
For multi-center studies or single site studies involving significant risk, an independent monitor 
may be required (e.g., monitoring by the staff of the PSU quality assurance program office(s) or 
by a clinical research organization). 
 
A co- investigator will monitor the study every few months. 
 
19.1.2 Safety Monitoring 
Include this section if FDA regulations apply to this study (see “WORKSHEET: Drugs (HRP-306)” 
and “WORKSHEET: Devices (HRP-307)”. HRP-306 and HRP-307 can be accessed by clicking the 
Library link in CATS IRB (http://irb.psu.edu).  
 
Indicate the process for identifying, recording and reporting adverse events. 
 
Specify roles for adverse event recording and monitoring. Indicate each staff member’s role in 
the adverse event reporting process. Include the following if applicable: 
 
The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the 
AE case report forms by the coordinator; be available to answer any questions that the 
coordinators may have concerning AEs; and will notify the IRB, FDA, sponsor and/or DSMB of all 
applicable AEs as appropriate. All assessments of AEs will be made by a licensed medical 
professional who is an investigator on the research. 
 
The Research Coordinator will complete the appropriate report form and logs; assist the PI to 
prepare reports and notify the IRB, FDA and/or DSMB of all Unanticipated Problems/SAE’s. 
 
The Monitor will confirm that the AEs are correctly entered into the case report forms. The 
Monitor will also confirm that the adverse events are consistent with the source documents and 
are reported to the appropriate regulatory bodies as required. 
 

Page 32 of 34 (V.01/21/2019)  
The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the 
AE case report forms by the coordinator; be available to answer any questions that the 
coordinators may have concerning AEs; and will notify the IRB, FDA, sponsor and/or DSMB of all 
applicable AEs as appropriate. All assessments of AEs will be made by a licensed medical 
professional who is an investigator on the research. 
 
The Research Coordinator will complete the appropriate report form and logs; assist the PI to 
prepare reports and notify the IRB, FDA and/or DSMB of all Unanticipated Problems/SAE’s. 
 
The Monitor will confirm that the AEs are correctly entered into the case report forms. The 
Monitor will also confirm that the adverse events are consistent with the source documents and 
are reported to the appropriate regulatory bodies as required. 
 
20.0 Future Undetermined Research: Data and Specimen Banking 
If this study is collecting identifiable data and/or specimens that will be banked for future undetermined 
research, please describe this process in the sections below.  This information should not conflict with 
information provided in section 22 regarding whether or not data and/or specimens will be associated with 
identifiers (directly or indirectly).  If NOT applicable, indicate as such below in all sections. 
[Do not type here] 
 
20.1 
Data and/or specimens being stored 
Identify what data and/or specimens will be stored and the data associated with each specimen. 
 
Not applicable. 
 
20.2 
Location of storage 
Identify the location where the data and/or specimens will be stored. 
 
Not applicable. 
 
20.3 
Duration of storage 
Identify how long the data and/or specimens will be stored. If data and/or specimens will be stored 
indefinitely, indicate as such.  
 
Not applicable. 
 
20.4 
Access to data and/or specimens 
Identify who will have access to the data and/or specimens. 
 
Not applicable. 
 
20.5 
Procedures to release data or specimens 
Describe the procedures to release the data and/or specimens, including: the process to request a 
release, approvals required for release, who can obtain data and/or specimens, and the data to be 
provided with the specimens. 
 
Not applicable. 
 

Page 33 of 34 (V.01/21/2019)  
20.6 
Process for returning results 
Describe the process for returning results about the use of the data and/or specimens. 
 
Participants will be instructed on what to do with their self-sampling kits when they receive the kit. 
 
21.0 References 
List relevant references in the literature which highlight methods, controversies, and study outcomes. 
 
1. Siegel, RL, Miller, KD, Jemal, A. Cancer statistics, 2018. CA Cancer J Clin 2018;68(1):7-30. 
2. US Preventive Services Task Force. Final recommendation statement: Cervical cancer: Screening. 2018; 
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/cervical-
cancer-screening2, 2018. 
3. Oeffinger KC, Fontham ETH, Etzioni R, et al. Breast Cancer Screening for Women at Average Risk: 2015 
Guideline Update From the American Cancer Society. JAMA. 2015;314(15):1599-1614. 
4. Benard VB, Thomas CC, King J, Massetti GM, Doria-Rose VP, Saraiya M, et al. Vital signs: Cervical cancer 
incidence, mortality, and screening – United States, 2007-2012. MMWR Morb Mortal Wkly 
Rep. 2014;63:1004–9. 
5. Wendy A. Leyden, M. Michele Manos, Ann M. Geiger, Sheila Weinmann, Judy Mouchawar, Kimberly 
Bischoff, Marianne Ulcickas Yood, Joyce Gilbert, Stephen H. Taplin, Cervical Cancer in Women With 
Comprehensive Health Care Access: Attributable Factors in the Screening Process, JNCI: Journal of the 
National Cancer Institute, Volume 97, Issue 9, 4 May 2005, Pages 675–
683, https://doi.org/10.1093/jnci/dji115 
6. Nelson EJ, Maynard BR, Loux T, et alThe acceptability of self-sampled screening for HPV DNA: a systematic 
review and meta-analysisSexually Transmitted Infections 2017;93:56-61. 
7.  Waller, J., Mccaffery, K., Forrest, S., Szarewski, A., Cadman, L., Austin, J., & Wardle, J. (2006). Acceptability 
of unsupervised HPV self-sampling using written instructions. Journal of Medical Screening, 13(4), 208–213. 
https://doi.org/10.1177/096914130601300409 
8. Szarewski, A., Cadman, L., Mesher, D. et al. HPV self-sampling as an alternative strategy in non-attenders for 
cervical screening – a randomised controlled trial. Br J Cancer 104, 915–920 (2011) doi:10.1038/bjc.2011.48 
9. Rees I, Jones D, Chen H, Macleod U (2018) Interventions to improve the uptake of cervical cancer screening 
among lower socioeconomic groups: a systematic review. Prev Med 111:323– 335. 
https://doi.org/10.1016/j.ypmed.2017.11.019 
10. Racey C, Withrow D, Gesink D. Self-collected HPV testing improves participation in cervical Cancer screening: 
a systematic review and meta-analysis. Can J Public Health. 2013;104(2):e159–e166. doi: 
10.1007/BF03405681 
11. Arbyn Marc, Smith Sara B, Temin Sarah, Sultana Farhana, Castle Philip. Detecting cervical precancer and 
reaching underscreened women by using HPV testing on self samples: updated meta-analyses BMJ 2018; 
363 :k4823 
12. Polman Nicole J, Ebisch Renée M F, Heideman Daniëlle A M, Melchers Willem J G, Bekkers Ruud L M, Molijn 
Anco C, Meijer Chris J L M, Quint Wim G V, Snijders Peter J F, Massuger Leon F A G, van Kemenade Folkert J, 
Berkhof Johannes. Performance of human papillomavirus testing on self-collected versus clinician-collected 
samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired 
screen-positive, non-inferiority trial. The Lancet Oncology. 2019;20(2):229–238. doi: 10.1016/S1470-
2045(18)30763-0. 
13.  Rees et al., Prev Med, 2018: https://www.sciencedirect.com/science/article/pii/S0091743517304607 
14. Arbyn Marc, Smith Sara B, Temin Sarah, Sultana Farhana, Castle Philip. Detecting cervical precancer and 
reaching underscreened women by using HPV testing on self samples: updated meta-analyses BMJ 2018; 
363 :k4823 
15. Polman Nicole J, Ebisch Renée M F, Heideman Daniëlle A M, Melchers Willem J G, Bekkers Ruud L M, Molijn 
Anco C, Meijer Chris J L M, Quint Wim G V, Snijders Peter J F, Massuger Leon F A G, van Kemenade Folkert J, 

Page 34 of 34 (V.01/21/2019)  
Berkhof Johannes. Performance of human papillomavirus testing on self-collected versus clinician-collected 
samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired 
screen-positive, non-inferiority trial. The Lancet Oncology. 2019;20(2):229–238. doi: 10.1016/S1470-
2045(18)30763-0. 
16. US Preventive Services Task Force. Screening for Cervical Cancer: US Preventive Services Task Force 
Recommendation Statement. JAMA. 2018;320(7):674–686. doi:10.1001/jama.2018.10897  
17. Spadea T., Bellini S., Kunst A., Stirbu I., Costa G. The impact of interventions to improve attendance in female 
cancer screening among lower socioeconomic groups: A review. Prev. Med. 2010;50:159–164. doi: 
10.1016/j.ypmed.2010.01.007. 
18. Racey, C.S., Withrow, D.R. & Gesink, D. Self-collected HPV Testing Improves Participation in Cervical Cancer 
Screening: A Systematic Review and Meta-analysis. Can J Public Health 104, e159–e166 (2013) 
doi:10.1007/BF03405681 
19. Mayrand M-H, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N 
Engl J Med. 2007;357(16):1579–88. https://www.nejm.org/doi/full/10.1056/NEJMoa071430 
20. Mayrand, Marie-Helene, Duarte-Franco, Aliane, Rodrigues, Isabel, Walter, Stephen, Hanley, James, Ferenczy, 
Alex, Ratman, Sam, Coutlee, Franciis, Franco, Eduardo. Human Papillomavirus DNA versus Papanicolaou 
Screening Tests for Cervical Cancer. The New England Journal of Medicine 
21. Polman, Nicole, Ebisch, Renee, Heideman, Danielle, Melchers, Willem, Bekkers, Ruud, Molijn, Anco, et al. 
Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the 
detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, 
non-inferiority trial. The Lancet Oncology’s 2019, 20(2): 229-238. 
22. Blake, KD, Moss, JL, Gaysynsky, A, et al. Making the case for investment in rural cancer control: An analysis 
of rural cancer incidence, mortality, and funding trends. Cancer Epidemiol Biomarkers Prev 2017. 
23. Moss, JL, Liu, B, Feuer, EJ. Urban/Rural Differences in Breast and Cervical Cancer Incidence: The Mediating 
Roles of Socioeconomic Status and Provider Density. Womens Health Issues 2017;27(6):683-691.