The Selfie Study- Assessing Novel Markers for Cervical Cancer Screening From Self-collected Samples
The Selfie Study- Assessing Novel Markers for Cervical Cancer Screening From Self-collected Samples
Cervical cancer is primarily caused by Human Papillomaviruses (HPV). Testing for HPV in
 cervical samples is now an option for cervical cancer screening. HPV can also be tested from
 self-collected samples which may help to improve access to screening, since it does not
 require a doctor visit. However, many women will test positive for HPV who are not at high
 risk for cervical cancer. Therefore, additional ("triage") tests are needed to determine
 which women testing HPV-positive require additional clinical workup. For self sampling, a
 triage test that could be measured from the same initial sample without requiring a follow-up
 visit to the doctor would be an ideal strategy. The purpose of this study is to determine
 whether a new HPV test that measures changes in HPV DNA can be used to triage HPV-positive
 women using self collected samples. This study will enroll 1,000 women who are undergoing
 cervical cancer screening at the George Washington University. Women will be asked to take a
 self-collected sample prior to their clinic visit. The investigators will evaluate the
 clinical accuracy of the new HPV triage test in self-collected samples and compare the
 accuracy of the test in samples collected by the clinician.
Worldwide, cervical cancer remains the fourth most common cancer and fourth leading cause of
 cancer deaths among women, with the greatest burden occurring in low-resource settings that
 lack effective screening and treatment. Even in the United States (U.S.), where Pap cytology
 screening has resulted in dramatic declines in cervical cancer incidence and mortality,
 thousands of new cases and related-deaths still occur every year, most commonly among
 underserved women who face barriers to accessing screening and/or treatment. The recent
 implementation of human papillomavirus (HPV) DNA testing as a primary strategy for cervical
 cancer screening has the potential to alleviate these disparities by improving the
 sensitivity for cervical precancer detection compared to Pap cytology, while providing
 greater long term reassurance following a negative HPV test. Moreover, HPV testing can be
 successfully performed on self-collected specimens, offering the possibility of expanding
 access to cervical cancer screening among hard-to-reach, underserved women.

 Despite the many advantages of primary HPV screening, the current challenge is optimizing
 triage testing to determine who among the many women testing HPV positive are at high-risk
 and require immediate colposcopy referral or treatment, while avoiding unnecessary harms
 among women at low-risk. A molecular triage test that can be conducted from the same primary
 screening sample (i.e., reflex testing) is particularly attractive for both high-and
 low-resource settings, particularly if it works from self-collected samples. Previously, DNA
 methylation of candidate host cell genes has been evaluated in self-collected samples and
 achieved acceptable performance for triage of HPV-positive women. In studies using clinician
 collected samples, there is a suggestion that methylation of carcinogenic HPV genotypes has
 better clinical performance (higher sensitivity/specificity) compared to host gene
 methylation; however, HPV methylation has not been evaluated in self-collected specimens.
 Because HPV DNA is present in only a small subset of infected cells in the lower genital
 tract, particularly in cervical precancers, it is likely that the signal-to noise ratio in
 self-collected samples is better for HPV compared to host gene methylation, resulting in
 improved specificity for cervical precancer detection. Evaluating the feasibility of HPV DNA
 methylation testing from self-collected samples is essential for determining the extent to
 which this assay can address the critical need for HPV triage in high- and low resource
 settings. In collaboration with the Cancer Genome Research Laboratory, a high-throughput,
 low-cost next-generation bisulfite sequencing assay that detects methylation of the 12 most
 carcinogenic HPV genotypes has been developed. Further, this assay includes a panel of host
 genes, including those that have been previously evaluated in self-collected specimens. The
 proposal is to test this assay in paired self and clinician-collected samples from 1,000
 women enrolled in an ongoing prospective study of women undergoing cervical cancer screening
 and colposcopy at the George Washington University (GWU). The hypothesis is that HPV and host
 DNA methylation will show non-inferior sensitivity and specificity for detection of cervical
 precancer in self-collected compared to clinician-collected samples and that HPV methylation
 will have higher absolute specificity compared to host methylation in both sample types.
Inclusion Criteria:

 -  Female

 -  Age 30-69

 -  Undergoing cervical cancer screening, diagnostic procedure (colposcopy), or treatment
 (LEEP)

 Exclusion Criteria:

 -  Pregnancy

 -  History of Cervical Cancer

 -  Prior hysterectomy

 -  Inability to provide informed consent