Cervical And Self-Sample In Screening Study
Cervical And Self-Sample In Screening Study
The proposed study seeks to compare the diagnostic performance of Human Papillomavirus (HPV)
 testing in self-collected samples via the Eve Medical self-collection system© (Eve) with
 standard physician-collected samples for the detection of cervical intraepithelial neoplasia
 grade 1 or worse (CIN1+) and cervical cancer among women referred for colposcopy. The
 performance of the Eve sample will also be compared with that of a second self-sample via a
 cobas® PCR Female swab.

 Approximately 1000 adult women with an abnormal Pap test at the level of an atypical squamous
 cells of undetermined significance or worse squamous or glandular abnormality (i.e., ASCUS+)
 or an abnormal co-test (ASCUS+ and HPV-positive) result will be recruited over a period of 12
 months via colposcopy clinics located at the Jewish General Hospital, St-Mary's Hospital, and
 the McGill University Health Centers (Royal Victoria Hospital).

 Participating women will undergo three cervical or cervicovaginal sampling techniques: 1)
 self-sampling using the Eve Medical self-collection system©; 2) self-sampling using a cobas®
 PCR Female swab; and 3) physician-collected sampling. The participants will also fill in a
 questionnaire on their experience with the convenience and acceptability of the Eve system,
 relative to the other two sampling approaches. The decision as to which self-sample is to be
 collected first will be dependent on randomization

 HPV testing will be done using the cobas® 4800 HPV Test. The liquid medium of within the
 cobas® PCR CELL Collection Media with the provider collected sample and the cobas® PCR media
 with the two self-collected samples will be used to suspend the cellular material prior to
 HPV testing. We have made collaborative arrangements with Dr. Marcel Behr, Chief of the
 Department of Clinical Microbiology at the McGill University Health Centre for the HPV
 genotyping work.

 Histology-confirmed CIN1+ will form the study outcome or case definition. Sensitivity,
 specificity, and predictive values (along with their respective 95% confidence intervals)
 will be calculated for each sample type to evaluate the clinical performance of the various
 sampling techniques. We will use CIN1+ as definition of disease but analyses will also be
 performed for more stringent definitions, e.g. CIN2+ or CIN3/cancer.
After the discovery that Human Papillomavirus (HPV) infection is the necessary cause of
 cervical cancer there have been much interest in the introduction of novel screening
 strategies involving HPV DNA testing [1]. HPV DNA testing was shown to have higher
 sensitivity in detecting cervical cancer and its precursors and greater reproducibility than
 Papanicolaou (Pap) cytology screening and has been therefore proposed as the primary
 screening method for the future. In high-income countries, cases of cervical cancer continue
 to develop among unscreened and under-screened women [2]. Factors discouraging women from
 attending routine screening include fear of pain or discomfort, lack of time or perceived
 inconvenience, cultural or religious concerns, and poor socioeconomic status [3]. For a
 screening program to be effective high coverage is essential and thus attendance is a
 critical requirement.

 Because of the high sensitivity of molecular HPV testing to detect cervical cancer precursors
 there is great potential for screening coverage to be increased by inviting non-attendant to
 provide self-collected vaginal samples. Providing these women with a simple, convenient, and
 inexpensive means of self-testing may improve cervical screening participation [3].
 Self-sampling is also an attractive approach to assist screening in poor countries, which
 typically do not have structured cervical cancer screening programs while having to bear the
 greatest burden of cervical cancer morbidity and mortality [4]. Self-sampling can also
 enhance the value of post-HPV vaccination surveillance by allowing a more efficient
 monitoring of HPV type distribution in populations. Finally, self-sampling represents a good
 research tool to assist prospective studies of genital HPV infection and natural history of
 cervical neoplasia.

 Specifically for cervical cancer screening, it has been shown that self-collected
 cervicovaginal specimens from women who received proper instruction for collecting them yield
 HPV test results that are comparable to those in specimens collected by physicians [5-8].
 Women also prefer self-sampling relative to clinician-provided samples, provided that they
 can be assured that they are told how to properly collect the sample [8, 9]. Although there
 is conceivably some loss of sensitivity and specificity in screening for cervical cancer in a
 specimen that is not directly collected from the ecto- and endo-cervix the overall accuracy
 of the HPV testing results (to identify presence of cervical precancerous lesions) is still
 superior to that of physician-collected Pap smears. Therefore, replacing a more
 anatomically-correct specimen (the one collected with direct visualization of the cervix by a
 primary healthcare provider) with one collected from the vagina (and thus diluted with
 exfoliated cells from a wider epithelial surface area) is compensated by the high sensitivity
 of the molecular screening approach [6, 10, 11]. Performance of screening seems also to be
 unaffected by storage and transport of the self-sample swabs, irrespective of whether they
 have been kept dry or transferred and resuspended into a liquid transport medium [10, 12].

 A critical feature in enhancing women's acceptance and adherence with the self-sampling
 approach for cervical cancer screening and HPV surveillance studies is the convenience of the
 device used for collection. Dacron and polyester swabs are simple, common, and inexpensive.
 However, they are inconvenient and not isolated within a sheath that prevents contact of the
 sampling area with mucosal surfaces in the labia and vaginal opening. Ideally, sampling
 devices should be anatomically correct to facilitate insertion and the sampling surface that
 will retain the exfoliated cells should be protected from contact with the labia and lower
 vaginal mucosa while the device is inserted, with the objective of sampling cells that are
 mostly from the cervix and upper vaginal area.

 HPV DNA testing using self-collected cervicovaginal specimens represents a promising strategy
 to increase cervical screening participation and thus reduce rates of cervical cancer in
 countries with established cervical screening programs. Furthermore, this approach can also
 greatly improve the coverage and quality of cervical cancer screening in developing
 countries, as well as in remote regions in developed countries, e.g., aboriginal populations
 in Northern Quebec and in First Nations territories. Facilitating and improving uptake of
 cervical cancer screening would save lives, reduce costs of treating invasive cancer and
 potentially reduce inequalities in avoidable mortality caused from cervical cancer.

 (full protocol available upon request)
Inclusion Criteria:

 -  Women of all ages are eligible to the study if they have been referred to the
 participating colposcopy clinic because of an abnormal Pap test at the level of an
 atypical squamous cells of undetermined significance or worse squamous or glandular
 abnormality (i.e., ASCUS+) or an abnormal co-test (ASCUS+ and HPV-positive) result.

 Exclusion Criteria:

 -  none