Elsevier

Papillomavirus Research

Volume 7, June 2019, Pages 67-74
Papillomavirus Research

Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women

https://doi.org/10.1016/j.pvr.2019.02.001Get rights and content
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Abstract

Background

Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1–4, B1–4, C1–4, D1–4) which may have differential cervical cancer risk.

Methods

A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI.

Results

A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1–4 and C1–4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0–4.7); A4 in East Asia (6.6, 3.1–14.1) and North America (3.8, 1.7–8.3); and D in North (6.2, 4.1–9.3) and South/Central America (2.2, 0.8–5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5–6.5; 12.1, 5.7–25.6, respectively).

Conclusions

HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal.

Abbreviations

ADC
adenocarcinoma/adenosquamous cell carcinoma
ASCUS
atypical squamous cells of undetermined significance
CI
confidence interval
CIN
cervical intraepithelial neoplasia
HPV
human papillomavirus
HC2
Hybrid Capture2
HSIL
high-grade squamous intraepithelial lesion
IARC
International Agency for Research on Cancer
ICO
Catalan Institute of Oncology
KPNC
Kaiser Permanente Northern California
LSIL
low-grade squamous intraepithelial lesion
NCI
National Cancer Institute
OR
odds ratio
SCC
squamous cell carcinoma

Keywords

HPV16
Cervical cancer
HPV carcinogenesis
HPV epidemiology
HPV genomics
Whole virus genome sequencing

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