Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral‐host interaction with implications for disease intervention

Abstract

HPV35 has been found in only 2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub-Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epidemiologic studies in the U.S. and internationally. Combining five U.S. studies, we measured HPV35 positivity and, in Northern California, observed HPV35 type-specific population

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women

“…To optimize the clinical performance of HPV testing in screening programs, our results indicate that only HPV 16,18,45,31,33,35,52, and 58 should be tested for. Although HPV 45 was not significantly associated with our disease endpoint, CIN2+, we include this genotype since it is the third most commonly identified genotype in invasive cervical carcinoma.…”

“…32 In particular, HPV35 was highly correlated to CIN2+/CIN3+ within our sample, which is consistent with recent studies that have found a strong link to cervical carcinogenesis for women of African ancestry with HPV35. 33 The GX platform is a pragmatic choice for South Africa given its current widespread usage across the country for tuberculosis testing 34 which offers potential leverage to utilize the same instruments for HPV screening. The global placements of the GX system now exceed 23 000 instruments, a large portion of which are in low resource settings (where TB is common), including Africa, Asia, and Latin America.…”

“…Specificity estimates improved for restricted vs full genotyping: 87.4% (full) vs 90.8% (restricted) in women without HIV and 63.7% (full) vs 71.4% (restricted) in women living with HIV. To optimize the performance of HPV testing for cervical cancer screening in high-burden, under-resourced settings like South Africa, only HPV 16,18,31,33,35,45,52, 58 could be included to define screen-positive. We recommend the inclusion of HPV45 for its known link to adenocarcinoma.…”

“…Genotyping for specific HPV genotypes could provide risk stratification of HPV-positive women by identifying HPV infections that are at highest risk of persisting and developing into invasive cervical cancer. 20,22 Of the approximately 40 HPV genotypes that affect the anogenital tract, 14 types (16,18,31,33,35,39,45,51,52,56,58,59,66,68) are considered high-risk for cervical cancer but vary in their degrees of oncogenicity. 23 HPV 16 and 18 are universally accepted as being the most carcinogenic (present in ~70% of invasive cancers).…”

“…[24][25][26] However, there is less consensus surrounding the relative importance of the other high-risk genotypes. 22 Based on the results from genotyping over 12 000 invasive anogenital cancers, the relative contribution of HPV 16,18,31,33,45,52, 58 to female anogenital cancer was found to be approximately 90% and, based on this, these are the high-risk genotypes incorporated in the nanovalent HPV vaccine. 27 This suggests that restricted genotyping could be effectively utilized to triage HPV-positive women in the context of screening.…”