November 04, 2017
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ART reduces HPV, cervical cancer in women with HIV

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Women with HIV on ART had a lower prevalence of high-risk HPV infection, high-grade cervical lesions and invasive cervical cancer than women who were not receiving ART, according to results of a recent meta-analysis.

“Our findings highlight the importance of early ART initiation (before reaching a low nadir CD4 cell count) and sustained effectiveness, as evidenced by duration, high adherence, virological control and CD4 cell recovery, in controlling HPV infection and cervical disease progression,” Helen Kelly, PhD, assistant professor in the clinical research department at London School of Hygiene and Tropical Medicine, and colleagues wrote in The Lancet HIV.

According to the researchers, women with HIV have a higher prevalence of high-risk HPV than the general population and are more likely to have persistent infection and progression of cervical intraepithelial neoplasia lesions. However, the impact of ART on HPV and cervical cancer is poorly understood.

The researchers conducted what they said was the first meta-analysis of its kind assessing the effect of ART on high-risk HPV, high-grade cervical lesion outcomes and invasive cervical cancer. Their analysis included cross-sectional and cohort studies published between Jan. 1, 1996, and May 6, 2017. Among the studies, 31 examined the association between ART and high-risk HPV (6,537 women with HIV) and cervical intraepithelial neoplasia of grade 2 or higher (CIN2+) or high-grade squamous intraepithelial lesions, or HSIL+ (9,288 women with HIV); 17 examined the effect of ART on longitudinal cervical lesion outcomes (6,864 women with HIV); and three examined the effect of ART on the incidence of invasive cervical cancer (15,826 women with HIV).

After adjusting for CD4 cell count and ART duration, Kelly and colleagues found that women receiving ART were less likely to have high-risk HPV (adjusted OR = 0.83; 95% CI, 0.7-0.99) and invasive cervical cancer (crude HR = 0.40; 95% CI, 0.18-0.87) than women not receiving ART. In addition, ART was associated with a reduced risk for HSIL-CIN2+ (aOR = 0.59; 95% CI, 0.4-0.87) and SIL progression (adjusted HR = 0.64; 95% CI, 0.54-0.75), and increased the likelihood of SIL or CIN regression (aHR = 1.54; 95% CI, 1.3-1.82).

Although most studies found a protective effect of ART on the incidence and progression of cervical lesions, fewer studies exist from Latin America and Asia and were less likely to report any protective association of ART. The researchers noted, however, that women enrolled in these studies may have received treatment based on older HIV guidelines that recommend initiating ART at lower CD4 cell count thresholds, and therefore may have a weakened HPV-specific mucosal immune response.

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“The current recommendation of encouraging earlier ART initiation, coupled with rapid virological control and sustained adherence is likely to lead to an earlier and possibly more functionally complete mucosal immune reconstitution,” they wrote. “We expect that this should in turn lead to a more rapid clearance of high risk HPV, thus reducing cytology diagnosed SIL and histology diagnosed CIN incidence or progression and ultimately reducing cervical cancer incidence in this high-risk population.”

In addition to initiating early ART, Kelly and colleagues recommended frequent HPV screening among women with HIV. In a related editorial, Henry J.C. de Vries, MD, PhD, professor at the University of Amsterdam and Renske D.M. Steenbergen, PhD, associate professor at VU University Medical Center, Amsterdam, called for the development of rapid point-of-care tests to improve screening programs in low- and middle-income countries with a high prevalence of HPV and HIV.

“Furthermore, future research in the line of Kelly and colleagues’ could be applied to anal cancer screening in HIV-positive men who have sex with men,” they added. “Triaging men for high resolution anoscopy to screen for anal precursor lesions would be welcomed for the same reason.” – by Stephanie Viguers

Disclosures: de Vries reports receiving grants from Merck. Steenbergen reports holding minority shares in Self-screen BV and has a patent for Methylation markers for cervical cancer detection. Kelly and colleagues report no relevant financial disclosures.