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

Abstract

Background: Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population.

Methods: A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa.

Results: In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%-25%), up to 41%-47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa.

Conclusions: HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women.

Keywords: cervical cancer; epidemiology; human immunodeficiency virus; human papillomavirus.

Figure 1.

Prevalence of human papillomavirus DNA among women infected with human immunodeficiency virus, by 8 cervical disease grades and region. (Disease grades including <10 tested women within an individual region are not shown.) Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; ICC, invasive cervical cancer; LSIL, low-grade squamous intraepithelial lesion.

Figure 2.

Positivity for human papillomavirus (HPV) types in women infected with human immunodeficiency virus (HIV) in Africa, as a proportion of HPV-positive samples (denominators in parentheses), by cervical disease grade for HPV types 16, 18, and 45 (A) 33, 58, 31, 52, and 35 (B), and 39, 59, 51, 56, and 68 (C). Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia (by grade); HSIL, high-grade squamous intraepithelial lesion; ICC, invasive cervical cancer; LSIL, low-grade squamous intraepithelial lesion.

Figure 3.

Positivity for human papillomavirus (HPV) types in women infected with human immunodeficiency virus (HIV) in Europe/North America, as a proportion of HPV-positive samples (denominators in parentheses), by cervical disease grade for HPV types 16, 18,and 45 (A), 33, 58, 31, 52, and 35 (B), and 39, 59, 51, 56, and 68 (C). Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia (by grade); HSIL, high-grade squamous intraepithelial lesion; ICC, invasive cervical cancer; LSIL, low-grade squamous intraepithelial lesion.