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. 2017 Feb 1;3(2):169-177.
doi: 10.1001/jamaoncol.2016.3067.

Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method

Gypsyamber D'Souza  1 , William H Westra  2 , Steven J Wang  3 , Annemieke van Zante  4 , Alicia Wentz  1 , Nicole Kluz  1 , Eleni Rettig  5 , William R Ryan  3 , Patrick K Ha  3 , Hyunseok Kang  6 , Justin Bishop  4 , Harry Quon  7 , Ana P Kiess  7 , Jeremy D Richmon  5 , David W Eisele  5 , Carole Fakhry  5
Affiliations

Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method

Gypsyamber D'Souza et al. JAMA Oncol. .

Abstract

Importance: Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear.

Objective: To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC).

Design, setting, and participants: Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used.

Main outcomes and measures: Outcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH.

Results: Of 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P < .001 for trend), as well as among whites (39% to 86%; P < .001 for trend) and nonwhites (32% to 62%; P = .02 for trend). Similar results were observed for ISH+ OPSCC (P ≤ .01 for all). Among 623 non-OP HNSCCs, a higher proportion were p16+ compared with ISH positive (62 [10%] vs 30 [5%]; P = .001). A high proportion (26 of 62 [42%]) of these p16+ non-OP HNSCCs were found in sites adjacent to the oropharynx. The proportion of p16+ and ISH+ non-OP HNSCCs were similar by sex. Over time, the proportion of non-OP HNSCCs that were p16+ (or ISH+) increased among whites (P = .04 for trend) but not among nonwhites (each P > .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity.

Conclusions and relevance: During 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.
Prevalence of Human Papillomavirus When Measured by p16 Immunohistochemical Positivity or by In Situ Hybridization (ISH) Positivity Among Patients With Oropharyngeal Squamous Cell Cancer (OPSCC) and Nonoropharyngeal Head and Neck Squamous Cell Cancer (non-OP HNSCC) (Oral Cavity, Larynx, and Nasopharynx Carcinoma) Over Time, by Sex A, P for trend for p16 positivity among OPSCC cases was .005 for women and <.001 for men. B, P for trend for ISH positivity among OPSCC cases was .01 for women and <.001 for men. C, P for trend for p16 positivity among non-OP HNSCC cases was .33 for women and .20 for men. D, P for trend for ISH positivity among non-OP HNSCC cases was .75 for women and .12 for men.
Figure 2.
Figure 2.
Prevalence of Human Papillomavirus When Measured by p16 Immunohistochemical Positivity or by In Situ Hybridization (ISH) Positivity Among Patients With Oropharyngeal Squamous Cell Cancer (OPSCC) and Nonoropharyngeal Head and Neck Squamous Cell Cancer (non-OP HNSCC) (Oral Cavity, Larynx, and Nasopharynx Carcinoma) Over Time, by Race and Ethnicity (Black Non-Hispanic, White Non-Hispanic, Hispanic of Any Race, and Asian Non-Hispanic) A, P for trend for p16 positivity among OPSCC cases was .16, <.001, .30, and .04 for 95 blacks, 103 whites, 21 Hispanics, and 21 Asians, respectively. B, P for trend for ISH positivity among OPSCC cases was .09, .002, .33, and .04 for blacks, whites, Hispanics, and Asians, respectively. C, P for trend for p16 positivity among non-OP HNSCC cases was .93, .04, .82, and .27 for 183 blacks, 214 whites, 78 Hispanics, and 148 Asians, respectively. D, P for trend for ISH positivity among non-OP HNSCC cases was .60, .06, .61, and .93 for blacks, whites, Hispanics, and Asians, respectively.
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