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, William H. Westra, Steven J. Wang, Annemieke Van Zante, Alicia Wentz, Nicole Kluz, Eleni Rettig, William R. Ryan, Patrick K. Ha, Hyunseok Kang, Justin Bishop, Harry Quon, Ana P. Kiess, Jeremy D. Richmon, David W. Eisele, Carole Fakhry

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 Outcomeswere 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.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalJAMA oncology
Volume3
Issue number2
DOIs
StatePublished - Feb 1 2017

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Squamous Cell Neoplasms
Head and Neck Neoplasms
In Situ Hybridization
Squamous Cell Carcinoma
Head
Neoplasms
Women's Rights
Oropharynx
Nasopharynx
DNA
Larynx
Mouth
Cohort Studies
Retrospective Studies
Demography
Sensitivity and Specificity
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

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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. / D'Souza, Gypsyamber; Westra, William H.; Wang, Steven J.; Van Zante, Annemieke; Wentz, Alicia; Kluz, Nicole; Rettig, Eleni; Ryan, William R.; Ha, Patrick K.; Kang, Hyunseok; Bishop, Justin; Quon, Harry; Kiess, Ana P.; Richmon, Jeremy D.; Eisele, David W.; Fakhry, Carole.

In: JAMA oncology, Vol. 3, No. 2, 01.02.2017, p. 169-177.

Research output: Contribution to journalArticle

D'Souza, G, Westra, WH, Wang, SJ, Van Zante, A, Wentz, A, Kluz, N, Rettig, E, Ryan, WR, Ha, PK, Kang, H, Bishop, J, Quon, H, Kiess, AP, Richmon, JD, Eisele, DW & Fakhry, C 2017, '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', JAMA oncology, vol. 3, no. 2, pp. 169-177. https://doi.org/10.1001/jamaoncol.2016.3067
D'Souza, Gypsyamber ; Westra, William H. ; Wang, Steven J. ; Van Zante, Annemieke ; Wentz, Alicia ; Kluz, Nicole ; Rettig, Eleni ; Ryan, William R. ; Ha, Patrick K. ; Kang, Hyunseok ; Bishop, Justin ; Quon, Harry ; Kiess, Ana P. ; Richmon, Jeremy D. ; Eisele, David W. ; Fakhry, Carole. / 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. In: JAMA oncology. 2017 ; Vol. 3, No. 2. pp. 169-177.
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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 Outcomeswere 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.",
author = "Gypsyamber D'Souza and Westra, {William H.} and Wang, {Steven J.} and {Van Zante}, Annemieke and Alicia Wentz and Nicole Kluz and Eleni Rettig and Ryan, {William R.} and Ha, {Patrick K.} and Hyunseok Kang and Justin Bishop and Harry Quon and Kiess, {Ana P.} and Richmon, {Jeremy D.} and Eisele, {David W.} and Carole Fakhry",
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TY - JOUR

T1 - 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

AU - D'Souza, Gypsyamber

AU - Westra, William H.

AU - Wang, Steven J.

AU - Van Zante, Annemieke

AU - Wentz, Alicia

AU - Kluz, Nicole

AU - Rettig, Eleni

AU - Ryan, William R.

AU - Ha, Patrick K.

AU - Kang, Hyunseok

AU - Bishop, Justin

AU - Quon, Harry

AU - Kiess, Ana P.

AU - Richmon, Jeremy D.

AU - Eisele, David W.

AU - Fakhry, Carole

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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 Outcomeswere 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.

AB - 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 Outcomeswere 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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