Dataset Information

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 HPV6-negative 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.

SUBMITTER: Sichero L

PROVIDER: S-EPMC6548638 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Sichero Laura L El-Zein Mariam M Ferreira Silvaneide S Franco Eduardo L EL Villa Luisa L LL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20190313 6

<h4>Background</h4>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.<h4>Methods</h4>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 equation ...[more]

PMID: 30867221

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Project description:To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, from October 2016 to March 2020, a total of 3,066 women were recruited for a 3-year prospective population-based cervical cancer screening clinical trial. The primary endpoint was histological cervical intraepithelial neoplasia 2 and worse (CIN2+). Twenty-nine SNPs of HPV receptor associated genes on women with available cytology residual samples at baseline were detected using MALDI-TOF MS. Eligible data were available for 2,938 women. Rs16894821 (GG versus AA, OR =1.71 [1.08 to 2.69]) and rs724236 (TT versus AA, OR = 1.73 [1.14 to 2.62]) in SDC2 were significantly related to the HPV susceptibility. And rs2575712 (TT versus GG, OR = 2.78 [1.22 to 6.36]) in SDC2 was associated with increased HPV 16/18 susceptibility. Four SNPs (rs1047057 and rs10510097 in FGFR2 gene, rs2575735 in SDC2 gene, and rs878949 in HSPG2 gene) were significantly associated with persistent HPV infection. Importantly, the genotypes of rs16894821 under recessive model (GG versus AA/AG, OR = 2.40 [1.12 to 5.15]) in SDC2 and rs11199993 under dominant model (GC/CC versus GG, OR = 1.64 [1.01 to 2.68]) in FGFR2 were significantly associated with the disease progression. Finally, SNPs showed comparable efficacy in detecting CIN2+ for the women infected with non-HPV16/18 compared with cervical cytology (sensitivity: 0.51 [0.36 to 0.66] versus 0.44 [0.30 to 0.60], specificity: 0.96 [0.96 to 0.97] versus 0.98 [0.97 to 0.99], positive predictive value: 0.23 [0.15 to 0.33] versus 0.33 [0.22 to 0.47], and negative predictive value: 0.99 [0.98 to 0.99] versus 0.99 [0.98 to 0.99]). SNPs in HPV receptor related genes may influence HPV susceptibilities and clinical outcomes in Chinese women. IMPORTANCE Virus receptors are known to mediate virus attachment and further lead to virus infection of the host cells. In the current study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, and to explore the new triaging strategy for non-16/18 high-risk HPV infection.

Project description:Genetic variation of 49 human papillomavirus (HPV) 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP) (n = 17), genital warts (n = 43), anal cancer (n = 6) and cervical neoplasia cells (n = 5), was determined by sequencing the long control region (LCR) and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65%) clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04). This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02). Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these HPV types.

Dataset Information

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

Publications

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

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