Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Behaviors and Mental Disorders

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Quality of Life

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Fluspirilene

HPV DNA testing

Conventional management (repeat Pap smear at 6 months)

Decision aid with choice of management

Kirsten McCaffery, PhD

Les Irwig, PhD

Glenn Salkeld, PhD

Alexandra Barratt, PhD

Kirsten Howard, Masters

Edith Weisberg, Medicine

The study compares the psychosocial outcomes of different management strategies for women with minor atypia (including 'HPV effect') detected on Pap smears: conventional management (a repeat Pap smear at 6 months) versus Human papillomavirus (HPV) DNA testing, a new method proposed for the management of minor atypia and the informed choice of either management supported by a decision aid.

The study examines women's informed preferences for each of these options and compares the psychosocial outcomes in women who are or are not given the choice of management.

HPV DNA testing offers considerable changes to the management of women with minor atypia and there is evidence from the USA which suggests that the use of HPV DNA testing as a triage strategy is effective for women within this group (Solomon et al 2001). The introduction of HPV DNA testing may bring both benefits and harms to women. These harms and benefits are not well understood. Examination of the psychosocial outcomes of HPV DNA testing compared to conventional management and women's preferences for each is needed to guide decisions concerning HPV DNA testing in cervical screening in Australia and also internationally.

Women diagnosed with minor atypia following a routine Pap smear will be randomised into one of the three management arms of the study (a) HPV DNA test, (b) Decision Aid (DA) with choice of management, or (c) a 6 month repeat Pap smear (conventional management). Women who are allocated to the HPV DNA arm and the repeat Pap will receive standard information about their management strategy. Women allocated to the decision aid arm will receive information about HPV DNA testing and 6 month repeat Pap in a decision aid format as an adjunct to usual clinical care and asked to indicate their preference for management. Women in this arm will receive the management strategy of their choice (HPV DNA or repeat Pap). The impact of the Decision Aid will be assessed and psychosocial impact of each management strategy will be followed up over the short, medium and long term.

Management and Clinical outcomes: Data will be collected on the taking and timing of Pap smears, HPV testing and colposcopy as well as findings for each of these tests and any subsequent treatment.

Psychosocial outcomes: Measures will be administered by postal questionnaire at multiple time points across the study. There will be 3 questionnaires: (1) Baseline questionnaire - for all participants recruited into the study; (2) Decision-making evaluation - to assess decision-making in all groups and the impact of the decision aid; (3) Psychosocial impact questionnaire - brief questionnaire (taking approximately 10 minutes to complete) sent at multiple time points to assess the psychosocial impact over time (2 weeks, 3, 6 and 12 months).

Quality of life assessment: Participants will be invited to take part in an interview at 1 month and 12 months post testing (HPV testing or repeat Pap smear) to assess quality of life using standardised validated QOL measures. Interviews will be carried out by an experienced female researcher. Study participants will be given the option to participate in the interview and will be under no obligation to take part if they do not wish to.

The IMAP Study Improving Management of Mildly Abnormal Pap Smears

HPV DNA Testing Versus Conventional Management for Women With Minor Atypia on Pap Smear: Psychosocial and Quality of Life Outcomes and Development of a Decision Analytic Model

National Health and Medical Research Council, Australia

Family Planning Association New South Wales

University of Sydney

Symptoms and General Pathology

Rare Diseases

Recurrence

Uterine Cervical Dysplasia

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Women randomized to this arm will undergo high risk HPV DNA testing using Hybrid Capture 2®.

Women will be followed in the colposcopy clinic as usual, with no standardized protocol, tests are left at the discretion of the treating physician, in order to document routine proactive. We will document all procedures (biopsies, endocervical curettage, cytology, etc) and their outcome.

Specimens will be collected with a cervical cytobrush and cervical cells will be resuspended in 2 ml of Preservcyt® (Hologic LP), a liquid cytology preservation media. 75µl of processed sample will be hybridized with 25 µl of probe B mixture. The assay is completed as a standard enzyme immunoassay with the addition of a dioxetane-based chemiluminescent substrate. Specimens will be considered positive for HPV if the ratio of RLUs of the specimen to the mean RLUs of triplicates of positive control (at 1 pg per ml or 5000 copies of HPV genome per test) is at least one.

high risk HPV DNA testing

Women will undergo colposcopy, with no standardized protocol; tests are left at the discretion of the treating physician, in order to document routine proactive. We will document all procedures (biopsies, endocervical curettage, cytology, etc) and their outcome.

Active comparator: Routine colposcopy

Marie-Hélène Mayrand, MD,PhD

This trial will compare HPV testing to the routine colposcopy in the follow-up of women treated for cervical high grade lesions. Women will be assigned randomly (by chance) after treatment of cervical pre-cancer to be either (1) followed-up by colposcopy, or (2) undergo HPV testing. Women found to have disease by either strategy will be offered re-treatment. For the next 2 years participants will undergo yearly, in depth, evaluation to assess the cervix for precancer. We will then be able to compare which of the 2 follow-up strategies worked best.

Background and rational: Cervical cancer ranks twelfth in terms of cancer mortality in Canadian women, but remains the second most frequent cancer in Canadian women aged 20-44. Fortunately, its natural history makes it an ideal candidate for successful prevention. Cervical cancer and its precursors are caused by a persistent infection of the cervical epithelium by one of the 15 oncogenic (or high risk) types of human papillomaviruses (HPVs). The preinvasive changes of cervical intra-epithelial neoplasia (CIN) can be identified through cervical cytology (also known as the Pap test). When cellular abnormalities are identified, women are referred for diagnostic testing. High-grade precursor lesions (CIN2/3) carry a high risk of progression to invasive cancer and for this reason their treatment is recommended. Treatment success rates of CIN2/3 are 85%. However, those who fail treatment need to be identified promptly because their risk of invasive disease is increased more then 10 fold. The current strategy used in Canada to identify treatment failures consists of a follow-up every 6 months in colposcopy clinics for 2 years. Recent research underlines the fact that routine colposcopy is unreliable and may miss significant lesions. The identification of oncogenic HPV DNA in the cervical secretions is known as HPV testing. A few studies have investigated the use of HPV testing in the identification of treatment failures. Although they point to a very good sensitivity (90-95%) there were methodological limitations: studies were small; the HPV test used was often not suitable for clinical laboratory use; endpoints were not assessed by histological confirmation. Most importantly, none compared HPV testing to colposcopy, the strategy used in Canada. Research question: Is HPV testing more sensitive than routine colposcopy to identify CIN2/3 treatment failures? Methodology: Design: We propose a parallel randomized controlled trial, where participants will be randomized 1:1 to routine colposcopy vs. HPV testing after treatment of CIN2/3 lesions. Study Population: Women treated for high-grade precursor lesions. Exclusion criteria are: pregnancy, less than 18 years of age, known immunosuppression or immunodeficiency, unable to provide informed consent. Study interventions: (1) HPV testing with Hybrid Capture 2. (2) Routine colposcopy. In order to evaluate the performance of the current follow-up strategy, there will be no standardized protocol for the colposcopy intervention, but documentation of procedures will be done. Patients will receive the study interventions 6 months after treatment. All participants will undergo expert diagnostic assessment at 12 and 24. Sample size calculation and recruitment rate. The sample size was calculated to have 80% power to detect an increase in sensitivity of 15%, with an alpha set at 0.05 (double sided test). Assuming a conservative baseline sensitivity of 70% for colposcopy, 134 cases of recurrent/persistent disease will be necessary in each study group. Assuming a 15% failure rate of treatment and a 20% drop out rate, a total of 2250 participants will need to be accrued. Recruitment will take place in high volume colposcopy clinics across Canada over 2 years. Analysis: The primary analysis will consist of the comparison of the diagnostic indices of the 2 follow-up strategies: sensitivity, specificity, positive and negative predictive values (with their 95% asymptotic confidence intervals). Cumulative persistent/recurrent cases identified during the 2 year follow-up will make up the case group. Since all participants will undergo expert diagnostic assessment. No subgroup analysis will be performed. 4. Expected contribution: The result from this trial will provide high quality data on which to base management recommendation. If HPV testing is found to be more sensitive than routine colposcopy, follow-up of treated lesion may occur mainly in primary care physician's office with HPV testing, reducing costs, and making it possible to focus colposcopy activities on a group of women truly at risk of significant disease.

Colposcopy Versus HPV Testing to Identify Persistent Cervical Precancers

Randomized Controlled Trial Comparing Routine Colposcopy to HPV Testing to Identify Persistent or Recurrent High Grade Cervical Cancer Precursors

Terry Fox Foundation

Canadian Institutes of Health Research (CIHR)

Centre hospitalier de l'Université de Montréal (CHUM)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The IMAP Study Improving Management of Mildly Abnormal Pap Smears	NCT00119509	Cervix Neoplasm...	HPV DNA testing Conventional ma... Decision aid wi...	18 Years - 70 Years	University of Sydney
Colposcopy Versus HPV Testing to Identify Persistent Cervical Precancers	NCT01051895	High Grade Cerv...	high risk HPV D... Active comparat...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Colposcopy Versus HPV Testing to Identify Persistent Cervical Precancers	NCT01051895	High Grade Cerv...	high risk HPV D... Active comparat...	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)

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