Human papillomavirus (HPV) is the root cause of more than 5% of cancers, including all cervical cancers and a substantial percentage of cancers at other sites.1 An estimated 63% of oropharyngeal cancers (OPCs) are caused by HPV; HPV type 16, the most common form, accounts for 90% to 95% of HPV-associated OPCs.2-7 More than 90% of OPCs are squamous cell cancers (SCCs) and are significantly more likely to be HPV-positive compared to other head and neck squamous cell cancers (HNSCC).4,7


Partly due to successful tobacco cessation efforts, the incidence of HPV-negative OPC is in decline; however, HPV-positive OPC rates are increasing with no sign of abating (Table 1).4-6,8 This is largely a result of differences in exposure behaviors—such as smoking and number of sexual partners—in middle-aged adults compared with their older birth cohorts.8


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Compared with HPV-negative OPC, HPV-positive OPC patients are disproportionately younger, male, nonsmokers, and nondrinkers. Although diagnosis at stage III/IV is common, with multi-node metastasis present, survival rates are better. On examination, tumors tend to be poorly differentiated, nonkeratinizing, and with basaloid morphology.5-7,13At current rates, OPC will become the leading HPV-associated cancer in the United States by the year 2020, surpassing the annual number of cervical cancers.5,6 Similar trends have been observed in other Western countries.5

Table 1. Incidence Rates of HPV-negative and HPV-positive Oropharyngeal Cancers6

Year HPV-positive HPV-negative  Overall
1988-1990 0.8 2.0 2.8
2003-2004 2.6 1.0 3.6
Incidence per 100,000 population.