RIS HPV TT Study Group: for list of members, see supplementary data.
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Original Paper
Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer
Article first published online: 12 NOV 2012
DOI: 10.1002/path.4065
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Additional Information
How to Cite
Geraets, D., Alemany, L., Guimera, N., de Sanjose, S., de Koning, M., Molijn, A., Jenkins, D., Bosch, X., Quint, W. and on behalf of the RIS HPV TT Study Group (2012), Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer. J. Pathol., 228: 534–543. doi: 10.1002/path.4065
Conflicts of interest: Daan Geraets has declared no conflicts of interest. Laia Alemany has received support for travel to meetings for study or other purposes (institutional) from Sanofi Pasteur MSD. Nuria Guimera has received support for occasional travel from GlaxoSmithKline, Merck and Qiagen. Silvia de Sanjose has declared that her research unit is involved in vaccine trials organized by GlaxoSmithKline and Merck/Sanofi Pasteur MSD and investigator-driven research partially sponsored by GlaxoSmithKline and Merck/Sanofi Pasteur MSD; travel funds to conferences/symposia/meetings were occasionally granted by either GlaxoSmithKline, Sanofi Pasteur MSD or Qiagen. Maurits de Koning has declared no conflicts of interest. Anco Molijn has received grants from GlaxoSmithKline. David Jenkins was previously an employee of GlaxoSmithKline and has received payment for consultancy from GlaxoSmithKline and MSD, and grants from MSD. Xavier Bosch has received payments for Advisory Board (GlaxoSmithKline, Merck Sharp & Dohme, Sanofi Pasteur MSD) and Speakers Bureau (GlaxoSmithKline) activities, and research grants (Merck Sharp & Dohme, Sanofi Pasteur MSD); his research unit is involved in vaccine trials organized by GlaxoSmithKline and Merck/Sanofi Pasteur MSD; and travel funds to conferences/symposia/meetings and honoraria are occasionally granted by GlaxoSmithKline, Merck, Sanofi Pasteur MSD, MTM or Qiagen. Wim Quint has received grants from GlaxoSmithKline
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RIS HPV TT Study Group: for list of members, see supplementary data.
Publication History
- Issue published online: 12 NOV 2012
- Article first published online: 12 NOV 2012
- Accepted manuscript online: 19 JUN 2012 04:22AM EST
- Manuscript Accepted: 9 JUN 2012
- Manuscript Revised: 29 MAY 2012
- Manuscript Received: 3 APR 2012
Keywords:
- human papillomavirus;
- carcinogenic;
- oncogenic;
- high-risk;
- cervical cancer;
- HPV26;
- HPV30;
- HPV67;
- HPV73;
- HPV82
Abstract
The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR–DEIA–LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.