Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies

Abstract

Background: Mucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences.

Methods: We performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference.

Results: Twenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]).

Conclusions: Our results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer.

Figure 1

Article identification and selection process for inclusion in the meta-analysis.

Figure 2

Pooled odds ratios estimating the oncogenic potential of each HPV genotype relative to HPV-16. NOTE: HPV genotypes were classified according to the International Agency for Research on Cancer [8,11], as follows: *Carcinogenic (Group 1), †probably carcinogenic (Group 2A), ‡possibly carcinogenic based on limited evidence in humans (Group 2B), ||possibly carcinogenic based on phylogenetic analogy to HPV genotypes with sufficient or limited evidence in humans (Group 2B), and §unclassifiable (Group 3). HPV-6, -11, -16, -18, -31, -33, -45, -52 and -58 are putatively included in the future nonavalent anti-HPV vaccine. Precise point estimates and 95% confidence interval limits illustrated in this figure are available in Table 2, columns 5 and 6.