Cervical And Self-Sample In Screening Study

Brief Title

Cervical And Self-Sample In Screening Study

Official Title

Cervical And Self-Sample In Screening (CASSIS) Study: Diagnostic Performance of Molecular HPV Testing With the Eve Medical Self-collection System© for Detecting Cervical Intraepithelial Neoplasia

Brief Summary

      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.
    

Detailed Description

      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)
    

Study Type

Interventional

Primary Outcome

Differences by comparison groups in detection of histologically confirmed Cervical Intraepithelial Neoplasia grade 1 or worse (CIN1+)

Secondary Outcome

 Patient satisfaction and experience using the self-sampling devices

Condition

Cervical Cancer

Intervention

Eve Medical self-collection system©

Study Arms / Comparison Groups

 Eve Medical self-collection system©

Description:  Device: Self-sampling swab from Eve Medical for collection of vaginal cells.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Device

Estimated Enrollment

1225

Start Date

June 2015

Completion Date

April 2016

Primary Completion Date

April 2016

Eligibility Criteria

        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
      

Gender

Female

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Eduardo Franco, DrPH, , 

Location Countries

Canada

Location Countries

Canada

NCT ID

NCT02397252

Organization ID

A11-M103-14B

Responsible Party

Principal Investigator

Study Sponsor

McGill University

Study Sponsor

Eduardo Franco, DrPH, Principal Investigator, McGill University

Verification Date

August 2016