Associations between highly active antiretroviral therapy and the presence of HPV, premalignant and malignant cervical lesions in sub-Saharan Africa, a systematic review: current evidence and directions for future research

Abstract

ObjectivesIn sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions.MethodFive databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities.Results22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3.ConclusionOur findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of invasive cervical cancer. Enhanced surveillance on the impact of HAART treatment is crucial.

Prevalence and Risk Factors of Cervical Dysplasia among Human Immunodeficiency Virus Sero-Positive Females on Highly Active Antiretroviral Therapy in Enugu, Southeastern, Nigeria

“…From our study, other categories, LSIL and HSIL were of lower prevalence compared to Dim et al, (2011) and reports from outside our study center on HIV+ve not on therapy, hence one can say that HAART reduces progression of cervical dysplasia among HIV+ve females, which is consistent with some previous reports (Minkoff et al, 2010;Alder et al, 2012;Firnhaber et al, 2012;Blitz et al, 2013;Ezechi et al, 2014;Katz et al, 2016). Firnhaber et al, (2012) concluded that HAART use reduced the rate of incidence and progression of cervical lesions among HIV+ve females and was dependent on duration of regimen but Menon et al, (2017), reported in their systematic review of effects of HAART on cervical dysplasia in sub Saharan Africa, suggested that CD4+ cell count may have a more instrumental role in cervical oncogenesis or the integration of the latent reservoir throughout the body than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. Minkoff et al, (2010) concluded that effective and adherent HAART use was associated with a significantly reduced burden of HPV infection and Squamous Intraepithelial Lesions (SILs).…”

A cross-sectional analysis of factors associated with detection of oncogenic human papillomavirus in human immunodeficiency virus-infected and uninfected Kenyan women

“…Three other studies of HIV-infected sub-Saharan women also indicate a positive impact of ART on reducing HR-HPV detection, as reviewed by Menon et al [30]. A meta-analysis also concluded that ART use, after adjusting for duration of use and CD4 count, was associated with reduced rate of HR-HPV in HIV-infected women [31].…”

Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology

“…8,9,16,213,214 Some evidence suggests that ART lowers the risk of persistent HPV infection and the prevalence of cervical intraepithelial neoplasia (CIN), precursors of cervical cancer. [215][216][217][218] However, evidence that the incidence of cervical cancer in WLWH has decreased significantly in the modern ART era is lacking. 8,10,12,17,127,219 In 2010, cervical cancer accounted for approximately 1% of cancers diagnosed in the HIV population.…”