Screen and Treat for Cervical Cancer Prevention
Screen and Treat for Cervical Cancer Prevention
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.
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.
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