Abstract
Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.
Highlights
Head and neck squamous cell carcinomas (HNSCC) have broadly varying rates of incidence and mortality around the world, with high rates notably in Southeast Asia and eastern Europe [1]
The NIH Pubmed search engine was employed to search for citations published through February 2004 using the MeSH terms ‘‘Papillomavirus’’ and ‘‘Head and Neck Neoplasms’’ in combination with keywords ‘‘polymerase chain reaction’’ or ‘‘PCR.’’ The inclusion criteria were (a) typespecific human papillomavirus (HPV) results from cancer tissue, (b) HPV results on a minimum of 40 cases of HNSCC or 20 cases of site-specific HNSCC, and (c) clearly described PCR-based HPV testing methods
Overall HPV prevalence was significantly higher in oropharyngeal SCCs (35.6%; 95% confidence intervals (95% CI), 32.6-38.7) than in oral SCCs (23.5%; 95% CI, 21.925.1) and laryngeal SCCs (24.0%; 95% CI, 21.8-26.3; Table 1)
Summary
Head and neck squamous cell carcinomas (HNSCC) have broadly varying rates of incidence and mortality around the world, with high rates notably in Southeast Asia and eastern Europe [1]. As detection of HPV DNA in tumor biopsies alone is not sufficient evidence of causation, molecular biology studies have helped identify a subset of these cancers that may be the consequence of HPV infection [5, 6, 9,10,11,12]. Such a subset is mainly found in the oropharynx, the tonsils
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