Screen and Treat for Cervical Cancer Prevention

NCT ID: NCT00233727

Last Updated: 2015-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 7123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2013-05-31

Brief Summary

The study measures the impact of "screen-and-treat" on the prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+). It is a three-arm, randomized clinical trial comparing two "screen-and-treat" approaches to delayed evaluation as a control. The primary outcome is biopsy-confirmed CIN 2+ at 6 months and significant complications within 6 months of randomization with continued follow-up to detect CIN2+ and other complications up to 36 months post-randomization.

Detailed Description

Participants and Clinical Examinations: Unscreened, non-pregnant women 35-65 years of age are enrolled at three closely located clinical sites in Khayelitsha, South Africa. All women provide informed consent, receive counseling for confidential HIV serotesting, a questionnaire, a pregnancy test if not postmenopausal, anonymous HIV serotesting, and a vaginal speculum examination by nurses trained in visual inspection of the cervix with acetic acid (VIA). Cervical specimens are obtained for testing for N. gonorrhea, Chlamydia trachomatis and high-risk types of HPV, and cytology. The cervix is washed with 5% acetic acid and inspected for gross abnormalities or areas of acetowhitening and a 35 mm. photograph taken. Women with significant cervicitis or vulvovaginitis are treated using the syndromic approach. N. gonorrhea or Chlamydia trachomatis positive women receive appropriate therapy. A positive VIA examination is defined as any acetowhite lesion and no attempt is made to differentiate the acetowhitening of metaplasia from CIN. Women with lesions suspicious for cancer, large acetowhite lesions extending over 70% of the cervix or into endocervical canal, and 374 unsuitable for cryotherapy due to severe atrophy, polyps, cervix distorted, cervix not adequately visualized are excluded. These women are referred to colposcopy.

Women are asked to return 2-6 days later for randomization to either: (1) HPV arm in which all HPV DNA positive women receive cryotherapy; (2) VIA arm in which all VIA positive women receive cryotherapy; and (3) a delayed evaluation arm in which women are followed untreated, irrespective of HPV or VIA status. Randomization is done at a patient level using a computer-generated randomization schedule with arm assignments provided to the clinics in sealed envelopes. Cryotherapy is performed by a nurse using N2O and a cryosurgical unit (Wallach Surgical Devices, Orange, CT) using two 3-minute freezes. Cytology results are not available at the time of cryotherapy. Both treated and untreated women are asked to return at 4 weeks for a questionnaire.

At 6 months, colposcopy is done by a physician blinded to arm and clinical information. All acetowhite lesions are biopsied and all have an endocervical curettage. Women with CIN 2+ are treated with LEEP. Examinations in women who became pregnant during the study are postponed until three months post-partum. Blood for anonymous HIV serotesting is obtained. All women who were HPV or VIA-positive at enrollment and a subset who were HPV and VIA-negative (all women enrolled in 2002) are scheduled for repeat colposcopy at 12 months, 24 months and 36 months post-randomization. At these visits, cervical samples are collected and colposcopy and biopsy if indicated is performed.

Laboratory Testing: HPV testing is done using the Hybrid Capture 2 HPV DNA assay and high-risk probe mixture (Digene Corporation, Gaithersburg, MD) at the University of Cape Town. Biopsies are processed at Columbia University and blindly evaluated by a single pathologist.

Conditions

Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

HPV DNA Testing + Cryosurgery

Patients will undergo a "Screen and Treat" program utilizing HPV DNA testing of clinician-collected cervical samples, followed by cryosurgery of screen positive women.

Group Type: ACTIVE_COMPARATOR

HPV DNA Testing + Cryosurgery

Intervention Type: PROCEDURE

Patients will undergo a "Screen and Treat" program utilizing HPV DNA testing of clinician-collected cervical samples, followed by cryosurgery of screen positive women.

VIA + Cryosurgery

Patients will undergo a "Screen and Treat" program utilizing visual inspection of the cervix with acetic acid (VIA), followed by cryosurgery of screen positive women.

Group Type: ACTIVE_COMPARATOR

VIA + Cryosurgery

Intervention Type: PROCEDURE

Patients will undergo a "Screen and Treat" program utilizing visual inspection of the cervix with acetic acid (VIA), followed by cryosurgery of screen positive women.

Delayed Evaluation and Treatment

Patients will undergo a similar screening process at entry, but will be randomized to have evaluation and treatment delayed until 6 months after screening.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

HPV DNA Testing + Cryosurgery

Patients will undergo a "Screen and Treat" program utilizing HPV DNA testing of clinician-collected cervical samples, followed by cryosurgery of screen positive women.

Intervention Type: PROCEDURE

VIA + Cryosurgery

Patients will undergo a "Screen and Treat" program utilizing visual inspection of the cervix with acetic acid (VIA), followed by cryosurgery of screen positive women.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Has a cervix
• Never been screened for cervical cancer
• Not currently pregnant

Exclusion Criteria

• Has previously had a Pap smear
• Has previously undergone treatment for cervical squamous intraepithelial lesion (SIL)
• Have lesions suspicious for cancer, have large acetowhite lesions extending over 70% of the cervix or into endocervical canal, are unsuitable for cryotherapy because of severe atrophy, polyps, cervix distorted, cervix cannot be adequately visualized
• Is unable to cooperate with study procedures or tolerate the insertion of a speculum

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

EngenderHealth

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lynette Denny, MD

Role: STUDY_DIRECTOR

University of Cape Town

Thomas C Wright, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

University of Cape Town

Cape Town, Western Cape, South Africa

Countries

South Africa

References

Denny L, Kuhn L, De Souza M, Pollack AE, Dupree W, Wright TC Jr. Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial. JAMA. 2005 Nov 2;294(17):2173-81. doi: 10.1001/jama.294.17.2173.

Reference Type: RESULT

PMID: 16264158 (View on PubMed)

Kuhn L, Wang C, Tsai WY, Wright TC, Denny L. Efficacy of human papillomavirus-based screen-and-treat for cervical cancer prevention among HIV-infected women. AIDS. 2010 Oct 23;24(16):2553-61. doi: 10.1097/QAD.0b013e32833e163e.

Reference Type: DERIVED

PMID: 20706107 (View on PubMed)

Other Identifiers

AAAB3373

Identifier Type: -

Identifier Source: org_study_id

NCT00494000

Identifier Type: -

Identifier Source: nct_alias