HPV-based screen-and-treat is effective for cervical cancer prevention in HIV-positive women
Polly Clayden, HIV i-Base
Louise Khun and colleagues report results from a trial of a simple cervical cancer prevention strategy using non-cytological screening methods – ie HPV DNA testing or visual inspection with acetic acid (VIA) – with immediate treatment where indicated for HIV-positive South African women, in a paper published ahead of print in AIDS.
The study authors note that it has been hard to establish conventional cytology based screening programmes in resource-limited settings. Yet, it is well known that HIV-positive women have high rates of human papillomavirus (HPV) and are at increased risk for developing cervical cancer. Furthermore as HIV-positive women are living longer on HAART, it is likely that more of these women will develop cervical cancer unless effective prevention strategies are put in place.
This was a randomised controlled trial of two screen-and-treat strategies of over 7000 non-pregnant women age 35-65 recruited from three clinics in Khayelitsha between January 2000 and December 2002.
Women were randomised into one of three study arms:
- HPV and treat – women with positive HPV test had cryotherapy
- VIA and treat women with positive VIA test had cryotherapy
- Control group evaluation or treatment was delayed for 6 months
All women were followed at 6 months after randomisation with colposcopy and biopsy.
The trail collected data on HIV status at baseline, 6, 12, 24 and 36 months. The investigators reported 956 women had an HIV-positive test at one of these visits.
This report showed findings from a comparison of the effects of screen and treat among women ever testing positive compared to women who remained negative throughout follow up.
The investigators conducted intent to treat analyses stratified by HIV status. The primary endpoint was cervical intraepithelial neoplasia grade 2 (CIN2+) or higher.
They found, out of the HIV-positive women, 148 in the HPV-and-treat group and 104 in the VIA-and-treat group had a positive test result and underwent cryotherapy. Among the HIV-negative women, 319 and 377 in the HPV and VIA groups respectively had a positive test. There were no significant differences between HIV-positive and HIV-negative women in rates of complications and side effects in those who had cryotherapy.
Using HPV DNA testing for screen-and-treat was highly effective in reducing the risk of CIN2+ by 36 months, both for HIV-positive, RR 0.20 (95% CI 0.06-0.69) and HIV-negative women, RR 0.31 (95% CI 0.20-0.50). The investigators observed less benefit for VIA-and-treat. This strategy reached statistical significance in HIV-positive women RR 0.51 (95% CI 0.29-0.89) but did not do so in HIV-negative women RR 0.76 (95% CI 0.52-1.1).
The investigators estimated, for every 100 women screened, HPV-and-treat programme could prevent 11.9 CIN2+ cases in HIV-positive women and 3.1 in HIV-negative women. VIA-and-treat programme could prevent 7.4 cases in HIV-positive women and 1.1 in HIV negative women.
Among the controls, higher rates of CIN2+ were detected by 36 months in HIV-positive than HIV-negative women, 14.9% vs 4.6%, p=0.0006.
The rates were reduced significantly in the HPV-and-treat group, 3.1% in HIV-positive women and 1.4% in HIV-negative women, p<0.0001. These reductions were less in the VIA-and-treat group, to 7.6% in HIV-positive women, p=0.002 and 3.5% in HIV-negative women, p=0.08.
The sensitivity in the control group of HPV DNA testing at enrollment to detect CIN2+ through 36 months, was 87% in HIV-negative women and 94.4% in HIV-positive women, compared to 47.8% and 63.9% respectively in the VIA group. The positive predictive value (PPV) for HPV testing was only slightly higher among HIV-positive women than HIV-negative women, 29.9% vs 22.7% HPV-positive at baseline had CIN2+ by 36 months. For VIA this was nearly three times higher in the HIV-positive than HIV-negative women. The investigators explained that this was due to 62.2% of HIV-positive women with positive VIA test also having had HPV DNA detected vs. 26.6% of HIV-negative women.
When they compared cryotherapy failure rates between HIV-positive and HIV-negative women, in the HPV-and-treat group, there was a slightly lower rate of CIN2+ after cryotherapy in HIV-positive (2.8%) vs HIV-negative (7.1%) women, p=0.05. In the VIA-and-treat group failure rates were similar in HIV-positive (4.8%) and negative (2.8%) women, p=0.43.
The investigators wrote: Our data provide proof-of-principle that HPV-based screen-and-treat is safe and effective in HIV-positive women. A single round of screening with an HPV test followed by cryotherapy of all screen-positive women reduced high-grade cervical cancer precursors (CIN2+) by 80%, and this reduction was sustained through 36 months.
Ref: Kuhn L et al. Efficacy of human papillomavirus-based screen and treat for cervical cancer prevention among HIV-infected women. AIDS 2010, published ahead of print 11 August 2010.