Human Papillomavirus-Based Cervical Cancer Prevention: Long-term Results of a Randomized Screening Trial

Department of Obstetrics and Gynecology, University of Cape Town, Cape Town, South Africa.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 09/2010; 102(20):1557-67. DOI: 10.1093/jnci/djq342
Source: PubMed

ABSTRACT Screen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial.
A total of 6637 unscreened South African women aged 35-65 years who were tested for the presence of high-risk human papillomavirus (HPV) DNA in cervical samples underwent visual inspection of the cervix using acetic acid staining and HIV serotesting. Of these, 6555 were randomly assigned to three study arms: 1) HPV-and-treat, in which all women with a positive HPV DNA test result underwent cryotherapy; 2) visual inspection-and-treat, in which all women with a positive visual inspection test result underwent cryotherapy; or 3) control, in which further evaluation or treatment was delayed for 6 months. All women underwent colposcopy with biopsy at 6 months. All women who were HPV DNA- or visual inspection-positive at enrollment, and a subset of all other women had extended follow-up to 36 months (n = 3639) with yearly colposcopy. The endpoint-cervical intraepithelial neoplasia grade 2 or worse (CIN2+)-was analyzed using actuarial life-table methods. All statistical tests were two-sided.
After 36 months, there was a sustained statistically significant decrease in the cumulative detection of CIN2+ in the HPV-and-treat arm compared with the control arm (1.5% vs 5.6%, difference = 4.1%, 95% confidence interval [CI] = 2.8% to 5.3%, P < .001). The difference in the cumulative detection of CIN2+ in the visual inspection-and-treat arm compared with the control was less (3.8% vs 5.6%, difference = 1.8%, 95% CI = 0.4% to 3.2%, P = .002). Incident cases of CIN2+ (identified more than 12 months after enrollment) were less common in the HPV-and-treat arm (0.3%, 95% CI = 0.05% to 1.02%) than in the control (1.0%, 95% CI = 0.5% to 1.7%) or visual inspection-and-treat (1.3%, 95% CI = 0.8% to 2.1%) arms.
In this trial, a screen-and-treat approach using HPV DNA testing identified and treated prevalent cases of CIN2+ and appeared to reduce the number of incident cases of CIN2+ that developed more than 12 months after cryotherapy.

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    • "HPV-DNA testing plus treatment with cryotherapy reduced the occurrence of CIN3+ by more than 77%, and VIA screening followed by cryotherapy reduced it by 38%, as compared to the control group with delayed treatment. Sensitivity for HPV-DNA and VIA was 90% and 53%, respectively, and specificity was 83% and 78% (Denny et al., 2010). Because HPV-DNA testing correctly identified both positive and negative women more often than VIA, using this test for screening was associated with less under-treatment as well as less over-treatment. "
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    • "In such settings, different strategies for managing the carcinogenic HPVpositive women may be implemented (Gage and Castle, 2010). For example, some programs may use an immediate screen-and-treat approach (Denny et al., 2010) without diagnostic verification of the presence of cervical pre-cancer by colposcopically directed biopsies, while other programs may require it. Of the latter, the prevalence of carcinogenic HPV DNA may be quite high, 10-20%, which may make colposcopy impractical in low-resource settings that have few trained colposcopists. "
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