Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis

Abstract

SummaryBackgroundThe interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes.MethodsWe did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546).FindingsWe identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70–0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40–1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40–0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54–0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30–1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18–0·87, I2=33%).InterpretationEarly ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect.FundingUK Medical Research Council.

Evaluation of anal carcinoma screening in male and female HIV patients at an interdisciplinary HIV therapy centre

“…In total, 17% of our subjects were female and seven female subjects showed mild to severe dysplasia in their screening assessment. As an increased risk of HPV‐mediated cervical and anal carcinoma in female PLWH has been reported, our result emphasizes that screening strategies for AIN should not neglect female PLWH . Unfortunately, our study did not include enough female PLWH to investigate risk factors specific to this patient group.…”

Cervical cancer risk in women living with HIV across four continents: A multicohort study

“…The extent to which ART protects women living with HIV from developing ICC is still being explored. Although ART reduces the prevalence of high‐risk HPV in women living with HIV and promotes regression of cervical lesions, many women in our analyses, notably in South Africa, may have started ART too late, when potentially irreversible precancerous cervical lesions were already present. Furthermore, not all women in our study would have achieved sustained suppression of HIV RNA, and high HIV RNA loads have been associated with an increased risk of HPV infection and cervical precancerous lesions .…”

“…The advent and scale‐up of combination antiretroviral therapy (ART) has led to a dramatic decline in morbidity and mortality from many HIV‐associated diseases, but these decreases have not occurred for ICC . Indeed, as life expectancy after starting ART increases, there is more time for precancerous cervical lesions to develop into ICC, but early initiation of ART seems to lower HPV coinfection rates and improve control of precancerous cervical lesions …”

“…6,7 Indeed, as life expectancy after starting ART increases, there is more time for precancerous cervical lesions to develop into ICC, but early initiation of ART seems to lower HPV coinfection rates and improve control of precancerous cervical lesions. 8 Global inequities in ICC incidence rates among women living with HIV have not been assessed previously. Our aim was to assess such inequities by comparing ICC incidence rates across different geographic regions among women who had initiated ART.…”

Incidence of cervical intraepithelial neoplasia in women infected with human immunodeficiency virus (HIV) with no evidence of disease at baseline: Results of a prospective cohort study with up to 6.4 years of follow‐up from India

“…It has been previously reported that HAART has little impact, if any, on the risk of CIN and cervical cancer screening must be integrated as a standard of care of HIV‐infected women . A recent systematic review and meta‐analysis of the association of ART and its effect on HPV, CIN and cervical cancer has reported that early initiation of HAART and its sustained adherence is likely to reduce incidence and progression of CIN in HIV‐infected women . But the authors have noted geographic variation in the risk.…”