HPV Detection in Head and Neck Squamous Cell Carcinomas: What Is the Issue?

Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes. Other modifications include: the reorganizing of skin cancer (other than melanoma and Merkel cell carcinoma) from a general chapter for the entire body to a head and neck-specific cutaneous malignancies chapter; division of cancer of the pharynx into 3 separate chapters; changes to the tumor (T) categories for oral cavity, skin, and nasopharynx; and the addition of extranodal cancer extension to lymph node category (N) in all but the viral-related cancers and mucosal melanoma. The Head and Neck Task Force worked with colleagues around the world to derive a staging system that reflects ongoing changes in head and neck oncology; it remains user friendly and consistent with the traditional tumor, lymph node, metastasis (TNM) staging paradigm. CA Cancer J Clin 2017;67:122-137. © 2017 American Cancer Society.

High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis. HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88). These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.

Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention.