ART reduces prevalence of cervical infection with high-risk HPV, pre-cancerous cell changes and cervical cancer

Antiretroviral therapy (ART) is associated with a lower prevalence of high-risk cervical human papillomavirus (HPV) infection in women with HIV, according to the results of a meta-analysis published in The Lancet HIV. Prevalence of high-grade pre-cancerous HPV-related cervical lesions and invasive cervical cancer was also lower among ART users.

“This is the first meta-analysis to investigate the associations between ART and high-risk HPV and cytology and histology diagnosed cervical lesions and invasive cervical cancer outcomes,” write the authors. “Our results indicate that women on ART had a lower prevalence of high-risk HPV and a reduction in the incidence of histology diagnosed HSIL-CIN2+ [high-grade squamous intraepithelial lesions-cervical intraepithelial neoplasia] and invasive cervical cancer, after adjustment for CD4 cell count and treatment duration.”

The authors believe that current recommendations for immediate ART and good adherence to treatment should reduce the incidence and progression of pre-cancerous lesions and ultimately cervical cancer in women with HIV.

Cervical cancer is one of the most common malignancies in women with HIV. Genital infection with HPV strains associated with a high risk of pre-cancerous cervical cell changes is more frequent in HIV-positive women. Moreover, women with HIV are more likely to have persistent infection with HPV and progression to CIN.

The effect of ART on the risk of high-risk HPV and cervical lesions is currently poorly understood. A team of investigators therefore undertook a meta-analysis of studies that explored these questions.

Studies conducted between 1996 and 2017 were eligible for inclusion if they reported the association of ART use with the following outcomes:

• Prevalence of cervical infection with high-risk HPV types.

• Prevalence, incidence, progression or regression of SIL or CIN.

• Cervical cancer incidence.

The authors identified 19 studies that reported on high risk HPV prevalence. The studies included a total of 6537 women, of whom 56% were currently on ART with a further 13% starting therapy. The pooled results showed that women on ART had a lower risk of high-risk HPV infection compared to women who were ART naïve (OR = 0.82; 95% CI, 0.68-0.98). Restricting analysis to studies that controlled for current or nadir CD4 cell count yielded similar results. Results from four studies that followed women starting ART provided strong evidence of reduced risk of prevalent high-risk HPV infection after ART initiation compared to before ART initiation (OR = 0.80; 95% CI, 0.72-0.89).

Longer duration of ART (two years or more) was also strongly associated with a reduction in high-risk HPV prevalence (OR = 0.65; 95% CI, 0.55-0.77).

There was some evidence that ART reduced the risk of HSIL-CIN2+, though the finding did not reach statistical significance (OR = 0.65; 95% CI, 0.40-1.06).

The effect of ART on the outcome of cervical lesions was reported in 17 studies involving 1830 women. Therapy was associated with a decreased incidence of SIL-CIN2 (OR = 0.59; 95% CI, 0.40-0.87). ART also reduced the risk of SIL progression (aHR = 0.64; 95% CI, 0.54 - 0.75) and also increased the likelihood of SIL or CIN regression (aHR = 1.54; 95% CI, 1.30-1.82).

Three studies involving approximately 16,000 HIV-positive women showed that ART significantly reduced the incidence of invasive cervical cancer (HR = 0.40; 95% CI, 0.18-0.87).

“The current recommendation of encouraging earlier ART initiation, coupled with rapid virological control, and sustained adherence is likely to lead to earlier and possibly more functionally complete mucosal immune reconstitution,” conclude the investigators. “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 and progression and ultimately reducing cervical cancer incidence…ART users with low or unknown nadir CD4 cell count remain at significant risk despite ART initiation and should be screened frequently.”

The authors of an editorial suggest that future research should investigate anal cancer screening for HIV-positive men who have sex with men.