Whole-genome sequencing analysis of HPV31 and HPV35 reveals variability in cervical cancer risk

Authors

• M Pinheiro
• Y Xiao
• M Yeager
• M Cullen
• JF Boland
• R Burk
• Z Chen
• K Yu
• N Wentzensen
• M Steinberg
• S Bass
• L Burdett
• T Raine-Bennett
• T Lorey
• PE Castle
• M Schiffman
• L Mirabello

Abstract

Background: HPV31 and HPV35 cause ~4% and 2% of cervical cancers worldwide, respectively. They are the closest genetically related to HPV16, responsible for ~60% of the cases. There are variant lineages linked to strong differences in carcinogenicity for HPV16, which is not known for HPV31 and HPV35. We investigated HPV31 and HPV35 genetic associations with risk of cervical precancer/cancer using HPV whole-genome sequencing data. Method: 2,073 HPV31 and 608 HPV35 cervical cell specimens from the NCI-KPNC PaP study were whole-genome sequenced using custom Ion AmpliSeq panels, including: CIN2 (HPV31=438; HPV35=179), CIN3-precancer (HPV31=342; HPV35=94), cancer (HPV31=7; HPV35=1) cases and controls with benign infections (=CIN1; HPV31=1,286; HPV35=334). Logistic regression models were used to estimate CIN3/cancer (CIN3+) risk and burden tests assessed the effects of rare variants (MAF

Scientific Focus Area: Genetics and Genomics

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