Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

Abstract

Objectives:HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type.Design:Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa.Method:Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR).Results:HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV.Conclusions:HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection.

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa

“…However, not all CIN2/3 develop into invasive cervical cancer (ICC), and not all HPV types found in CIN2 have the same propensity to evolve towards ICC. Clifford et al, in their systematic review comparing the HPV type distribution in ICC biopsy and cervical specimens of 770 HIV-positive women from 21 studies in 12 African countries [29], report a higher pooled prevalence of HPV16/18 (61.7%) than found in this study, whilst the prevalence of the other nonavalent vaccine types was 11.2%, lower than what we report in our study. These findings indicate that the relative contribution of HPV16/18 increases with increasing lesion grade, whilst the contribution of the additional nonavalent vaccine still represents a significant preventable fraction of ICC.…”

Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

“…Indeed, 358 African WHIV with ICC were previously compared with 790 African women with ICC in the HIV-uninfected population from the same 7 studies [17], showing that HIV infection does indeed alter the relative carcinogenicity of HR HPV types: the fraction of ICC caused by HPV 16 was significantly lower, and that of HPV 18 concomitantly higher, in HIV-positive women.…”

“…Of note, the 770 ICC cases from Africa have been described in depth, and compared with ICC cases in HIV-negative subjects from the same continent, in a previous publication [17]. …”

HIV-associated malignancies in sub-Saharan Africa

“…Moreover, the quadrivalent vaccine which has been most widely adopted is less immunogenic in HIV-infected women with severe immunosuppression [39], and vaccination has yet to be applied in most LMIC to at-risk populations other than school-age girls, including boys. The quadrivalent vaccine also provides limited protection against oncogenic HPV subtypes other than 16 and 18, with non-16/18 subtypes being responsible for approximately 20% of cervical cancer globally [40], although the proportion of cases attributable to 16/18 versus non-16/18 HPV subtypes does not appear to differ in SSA by HIV status [41**]. …”