Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell carcinoma.
Recent studies have found that cases with oropharyngeal squamous cell carcinoma (OPSCC) positive for HPV16 genotype have better overall survival compared with cases positive for other HPV genotypes. We sought to further replicate these studies and determine if this relationship is modified by expression of p16 tumor suppressor protein.



We identified 238 OPSCC cases from the Carolina Head and Neck Cancer Study (CHANCE) study, a population based case-control study. Tumors that tested positive solely for HPV16 genotype and no other genotypes with PCR were classified as HPV16-positive. Tumors positive for any other high-risk HPV genotype were classified as non-HPV16-positive. Expression of p16 in the tumor was determined with immunohistochemistry. Follow-up time was calculated from the date of diagnosis to date of death or December 31, 2013. Overall survival was compared with the Kaplan-Meier curves and log-rank test. Hazard ratios (HR) adjusted for smoking, alcohol use, sex, race, and age was calculated with the Cox proportional hazard regression.



Cases with HPV16-positive OPSCC had better overall survival than cases with non-HPV16-positive OPSCC (log-rank p-value: 0.010). When restricted to OPSCC cases positive for p16 expression, the same trend continued (log-rank p-value: 0.002). In the adjusted model, cases with non-HPV16-positive OPSCC had greater risk of death compared to cases with HPV16-positive tumors (HR: 1.92; 95% CI: 1.03, 3.60).



This finding indicates that HPV genotyping carries valuable prognostic significance in addition to p16 status and future survival studies of OPSCC should take into account differing HPV genotypes.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address: amazul@unc.edu.
Angela L
AL
Mazul
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Nidia
N
Rodriguez-Ormaza
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States.
James M
JM
Taylor
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States.
Dipan D
DD
Desai
International Agency for Research on Cancer (IARC), Lyon, France.
Paul
P
Brennan
International Agency for Research on Cancer (IARC), Lyon, France.
Devasena
D
Anantharaman
International Agency for Research on Cancer (IARC), Lyon, France.
Tarik
T
Gheit
International Agency for Research on Cancer (IARC), Lyon, France.
Massimo
M
Tommasino
International Agency for Research on Cancer (IARC), Lyon, France.
Behnoush
B
Abedi-Ardekani
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Andrew F
AF
Olshan
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jose P
JP
Zevallos
D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D030361:Papillomavirus Infections / Q000821:virology*; D016016:Proportional Hazards Models; D016019:Survival Analysis
HPV; HPV16; Head and neck cancer; Oropharyngeal cancer; p16
Head Neck. 2016 Sep;38(9):1330-7
27080140
Br J Cancer. 2015 Mar 17;112(6):1098-104
25688737
Br J Cancer. 1995 Sep;72(3):646-9
7669576
Infect Agent Cancer. 2012 Feb 29;7:4
22376902
J Clin Oncol. 2014 Oct 20;32(30):3365-73
24958820
JAMA Oncol. 2016 Jun 1;2(6):823-6
27010835
Clin Oncol (R Coll Radiol). 2013 Nov;25(11):630-8
23916365
Eur J Cancer. 2015 Dec;51(18):2759-67
26602016
J Clin Oncol. 2011 Nov 10;29(32):4294-301
21969503
Cochrane Database Syst Rev. 2015 Dec 01;(12):CD010341
26625332
J Adolesc Health. 2010 Apr;46(4 Suppl):S20-6
20307840
Am J Surg Pathol. 2010 Aug;34(8):1088-96
20588174
Methods Mol Biol. 2014;1180:237-55
25015151
Ann Oncol. 2014 Nov;25(11):2101-15
25057165
Ann Oncol. 2014 Jul;25(7):1410-6
24799460
Oral Oncol. 2016 May;56:47-53
27086486
Virology. 1991 Mar;181(1):374-7
1847260
J Clin Microbiol. 2010 Jan;48(1):143-9
19864475
J Virol. 2009 Nov;83(22):11784-94
19740985
Cancer. 2015 Feb 15;121(4):535-44
25283642
J Natl Cancer Inst. 2016 Jan 28;108(6):djv403
26823521
Oral Oncol. 2015 Feb;51(2):119-23
25467774