Lack of Association between Human Papillomavirus Types 6 and 11 Genetic Variants and Cervical Abnormalities: The Ludwig–McGill Cohort Study

Abstract

Background: Human papillomavirus (HPV) types 6 and 11 are mainly associated with the development of genital warts and recurrent respiratory papillomatosis. We examined intratypic genetic variability of both viral types with the development of cervical cytologic abnormalities in Brazilian women.Methods: We used PCR sequencing to characterize variants of HPVs 6 and/or 11 in cervical swabs from women in the Ludwig-McGill Cohort Study. We used a binomial generalized estimating equations (GEE) model with logit link to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV 6 and 11 variants and cytologic abnormalities.Results: B1 and B3 HPV6 and A2 HPV11 variants were the most common isolates identified. Compared with HPV6negative women, the ORs among women harboring HPV6 B1 or B3 variants were 6.3 (95% CI, 2.3-17.0) and 2.3 (95% CI, 0.6-9.7) for atypical cells of undetermined significance (ASCUS)/low squamous intraepithelial lesions (LSIL), respectively, and 1.7 (95% CI, 0.6-5.1) and 1.2 (95% CI, 0.3-4.7) for ASCUS/LSIL/high squamous intraepithelial lesions (HSIL). Respective ORs were 5.0 (95% CI, 1.7-14.6) and 2.8 (95% CI, 1.0-8.1) upon comparing women with HPV11 A2 variants to HPV11-negative women. All associations disappeared when adjusting for coinfections with high-risk HPV types.Conclusions: Our data do not support an association between low-risk HPVs 6 and 11 genetic variability and cervical abnormalities.Impact: Risk of cervical cytologic abnormalities is not affected by intratypic polymorphism in HPVs 6 and 11.

Prevalence of human papillomavirus 6 and 11 variants in recurrent respiratory papillomatosis

“…22 We also evaluated the frequency and clinical correlates of HPVs 6 and 11 variants infection in 79 and 39 women enrolled to the Ludwig/McGill cohort study, 41 respectively, throughout a follow-up period up to 10 years, and observed that cervical cytological abnormalities were not affected by HPV intratypic heterogeneity. 23 It needs to be highlighted that within these women we were unable to characterize the molecular variant in 22.5% of the smears, and that solely 17 and 5…”

“…On contrary, within 89 HPV‐11 positive HIM participants (42 developed GWs) among whom variants from the A2 sublineage were the more frequently detected, no association of specific variants with the clinical disease was observed 22 . We also evaluated the frequency and clinical correlates of HPVs 6 and 11 variants infection in 79 and 39 women enrolled to the Ludwig/McGill cohort study, 41 respectively, throughout a follow‐up period up to 10 years, and observed that cervical cytological abnormalities were not affected by HPV intratypic heterogeneity 23 . It needs to be highlighted that within these women we were unable to characterize the molecular variant in 22.5% of the smears, and that solely 17 and 5 HPVs 6 and 11 positive women developed ASCUS (atypical cells of undetermined significance) or LSIL during the study period, respectively.…”

“…We recently described that whereas in men HPV‐6 B1 variants are associated with a higher risk of developing GW compared with non‐B1 variants, 21 GW risk was not affected by HPV‐11 intratypic variability 22 . Moreover, we observed no association between HPVs 6 and 11 genetic variants and cervical low‐grade squamous intraepithelial lesions (LSIL) 23 . These data prompted us to assess the influence of HPVs 6 and 11 genetic heterogeneity upon RRP development.…”

“…22 Moreover, we observed no association between HPVs 6 and 11 genetic variants and cervical lowgrade squamous intraepithelial lesions (LSIL). 23 These data prompted us to assess the influence of HPVs 6 and 11 genetic heterogeneity upon RRP development. In the current work, we thought to describe the distribution of HPVs 6 and 11 variants in a series of JORRP and AORRP laryngeal papillomas and to evaluate the clinical correlates associated with these infections.…”