Human Papillomavirus Prevalence in Oropharyngeal Cancer Before Vaccine Introduction, United States

Martin Steinau; Mona Saraiya; Marc T. Goodman; Edward S. Peters; Meg Watson; Jennifer L. Cleveland; Charles F. Lynch; Edward J. Wilkinson; Brenda Y. Hernandez; Glen Copeland; Maria S. Saber; Claudia Hopenhayn; Youjie Huang; Wendy Cozen; Christopher Lyu; Elizabeth R. Unger


Emerging Infectious Diseases. 2014;20(5):822-828. 

In This Article


Of the 1,271 oropharyngeal tumors requested from the participating cancer registries, samples from 588 case-patients were received and successfully tested. Those not received were either unavailable or the remaining tissue was not representative of disease. The demographic characteristics (sex, age) and cancer stage (Table 1)[22] of the cohort from which the tested sample set was collected were similar to those of the untested cohort. Persons from the Asian Pacific Islands were few in number and slightly overrepresented in the final test population.

HPV results for 476 (81.0%) samples were from the linear array and 112 (19%) from LiPA. Most tissue was from the primary site (n = 473), but for 15 samples, only metastatic tissue from lymph nodes was available. Most case-patients (77.6%) were from urban areas or counties with a population >250,000. Most (94.4%) diagnoses were made during 2000 or later. Median age at the time of diagnosis was 58 (range 28–97) years. The male-to-female ratio was 3:1 and most of the cases (75.6%) were in non-Hispanic White persons. SCC, the most common histologic type of oropharyngeal cancer, accounted for 557 (94.7%) of all cases, and the main analysis was restricted to these cases (Table 2).

HPV was detected in 403 of the 557 OPSCC cases (72.4%) with valid typing results and 396 (71.1%) were positive for >1 high-risk type (Table 3). In 68.4% of cases, a single HPV type was found; 3.9% contained 2 types. In 7 cases, only low-risk HPV types were detected: HPV-11, 26, 69, 82 (2 cases), 83, and HPV-X). HPV-16 was present in 337 (60.5%) cases, HPV-18 in 14 (2.5%) cases, and 331 (59.4%) cases were exclusively positive for these 2 types.

Other high-risk types, including HPV-31, 33, 35, 39, 45, and 52, were found at low frequency (Table 3). The relative prevalence in case-patients that had multiple HPV types essentially followed single–type distributions. HPV-16/33 was the most frequent combination (6 cases); HPV-16/18 and HPV-16/31 were the next most frequent, found in samples from 3 case-patients each. Frequencies of all co-detected HPV types are shown in Table 4. More than 2 types were not found in any of the oropharyngeal cancers.

Proportions of high-risk HPV prevalence and HPV-16/18 were statistically different among the registries and by race/ethnicity, stage, and anatomic subsite (Table 2). By sex, prevalence was only different for those infected with HPV-16/18. Age at diagnosis was not statistically different between the stratified groups, but median age at diagnosis among high-risk HPV positive case-patients was 58 (28–92) years and 61 (36–97) years in high-risk negative case-patients (p = 0.023).

According to hierarchical assessment, HPV-16 was found in 337 (60.5%) OPSCC cases, HPV-18 in 11 (2.0%), other 9-valent high-risk types in 32 (5.7%), other high-risk types in 16 (2.9%), and low-risk types in the remaining 7 (1.3%) cases (Figure 1). Of the 15 case-patients for whom lymph node metastases were tested, 14 were positive for high-risk HPV and 13 were positive for HPV-16.


Hierarchical designation of human papillomavirus (HPV) types to oropharyngeal squamous cell carcinomasWhite sections of bars indicate attribution of the specific HPV type or groupBlack sections of bars indicate cumulative prevalence of types in higher hierarchyHPV-16 includes all cases positive for this type regardless of other resultsHPV-18 includes all cases positive for HPV-18, but negative for HPV-16Cases of 9-valent HPV with high-risk HPV types included in the candidate 9-valent HPV vaccine: HPV-31, -33, -45, -52, -58, but not HPV-16 or -18High-risk: cases positive for any high-risk type not included in the previous categories: HPV-35, -39, -51, -66, -68Low-risk: cases only positive for HPV types with low or no oncogenic potential.

In multivariate analysis for high-risk HPV that included age and sex in the model, only race/ethnicity was a significant independent factor (p = 0.003). Odds for high-risk HPV infections were significantly higher for all other race groups than for non-Hispanic Black persons (p<0.001). When only HPV-16/18 detection was considered, significant differences were found in sex (p = 0.009) and race/ethnicity in (p<0.001), but not age (p = 0.063), between those infected and those who were not (Table 5).

The 31 cases that had histologic results other than SSC included 7 adenocarcinomas (2 were HPV-16 positive, 5 HPV negative) and 2 small cell or neuroendocrine carcinomas (both HPV negative). Twenty-two cases were carcinomas not further specified, of which 7 tested positive for HPV (4 for HPV-16, and 1 each for HPV-18, HPV-33, HPV-35).