Exploring the Role of HPV 16 in Squamous Cell Cancers of Oral Cavity and Oropharynx

Koray Tümüklü; Fatih Çelenk; İsmail Aytaç; Ercan Kurt; Muzaffer Kanlıkama

doi:10.54614/eurjther.2021.0042

Authors

Koray Tümüklü Department of Otorhinolaryngology, Sanko University, Faculty of Medicine, Gaziantep, Turkey https://orcid.org/0000-0001-8821-4457
Fatih Çelenk Department of Otorhinolaryngology, International Medical Center IMC Hospital, Mersin, Turkey https://orcid.org/0000-0002-7557-7854
İsmail Aytaç Department of Otorhinolaryngology, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey https://orcid.org/0000-0002-0947-366X
Ercan Kurt Department of Otorhinolaryngology, Adıyaman Training and Research Hospital, Adıyaman, Turkey https://orcid.org/0000-0003-2595-0873
Muzaffer Kanlıkama Department of Otorhinolaryngology, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey https://orcid.org/0000-0002-3537-7778

DOI:

https://doi.org/10.54614/eurjther.2021.0042

Keywords:

Oral cavity, oropharynx, neoplasms, human papillomavirus p16, immunohistochemistry

Abstract

Abstract: Objective: Human papillomavirus infections may have a role in the development of oral cavity and oropharynx carcinomas. Human papillomavirus-positive oral cavity and oropharyngeal carcinomas differ from human papillomavirus-negative in that to occur in younger, are more frequent in men, and are strongly associated with sexual behavior. These observations lead to the treatment options and outcomes in human papillomavirus-related tumors, and the questions of targeted treatment that can be performed in the coming years have come to age.

Methods: This prospective study was conducted at Gaziantep University, medical faculty, otorhinolaryngology department. Patients with squamous cell carcinomas of non-lip oral cavity and oropharyngeal admitted to our department were included in the study. Samples from the cases were immunohistochemically stained. Sections were examined by light microscopy.

Results: The 55 cases P16 (76.4%) expressions were detected to be positive, and 17 (23.6%) cases were negative. There was no statistically significant correlation between prognostic parameters and p16 expressions. However, a significant difference was detected between human papillomavirus-positive and negative groups in regard to survival in oropharyngeal carcinoma.

Conclusion: Disease management can consider human papillomavirus-positive oral cavity and oropharyngeal carcinomas as a separate group. human papillomavirus-positive oral cavity and oropharyngeal carcinomas respond better to chemotherapy and radiotherapy than human papilloma virus-negative cancers. The presence/absence of human papillomavirus 16 might be considered a prognostic marker, but its reliability has not yet been confirmed. In future clinical studies, cancer centers should classify head–neck patients with respect to human papillomavirus status. However, we must always emphasize that the best treatment for cancer in which the main pathogenic agent is known is protection.

Metrics

Metrics Loading ...

References

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-2917.

Sturgis EM, Ang KK. The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms? J Natl Compr Canc Netw. 2011;9(6):665-673.

Gillison ML, D'Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407-420.

Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781-789.

Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467-475.

Shope RE, Hurst EW. Infectious papillomatosis of rabbits: with a note on the histopathology. J Exp Med. 1933;58(5):607-624.

Carcopino X, Henry M, Olive D, Boubli L, Tamalet C. Detection and quantification of human papillomavirus genital infections: virological, epidemiological, and clinical applications. Med Mal Infect. 2011;41(2):68-79.

Snijders PJF, Van den Brule AJC, Meijer CJLM, Walboomers JM. Papillomaviruses and cancer of the upper digestive and respiratory tracts. Curr Top Microbiol Immunol. 1994;186:177-198.

Brandwein MS, Nuovo GJ, Biller H. Analysis of prevalence of human papillomavirus in laryngeal carcinomas. Study of 40 cases using polymerase chain reaction and consensus primers. Ann Otol Rhinol Laryngol. 1993;102(4 Pt 1):309-313.

Mendenhall WM, Tannehill SP, Hotz MA, Kásler M, Remenár E. Should chemotherapy alone be the initial treatment for glottic squamous cell carcinoma? Eur J Cancer. 1999;35(9):1309-1313.

Taxy JB. Upper respiratory tract. In: Anderson's Pathology. 10th ed. St. Louis: Mosby; 1996:1460-1469.

Gnagy S, Ming EE, Devesa SS, Hartge P, Whittemore AS. Declining ovarian cancer rates in U.S. women in relation to parity and oral contraceptive use. Epidemiology. 2000;11(2):102-105.

Shiboski CH, Schmidt BL, Jordan RC. Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20-44 years. Cancer. 2005;103(9):1843-1849.

Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.J Natl Cancer Inst. 2000;92(9):709-720.

Gillison ML. Human papil lomav irus- assoc iated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744-754.

Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papil lomav irus- assoc iated head and neck cancer based on a prospective clinical experience. Cancer. 2010;116(9):2166-2173.

Frega A, Manzara F, Schimberni M, et al. Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users. Eur Rev Med Pharmacol Sci. 2016;20(17):3528-3534.

Adelstein DJ, Ridge JA, Gillison ML, et al. Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9-10,2008, Washington, D.C. Head Neck. 2009;31(11):1393-1422.

Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984;3(5):1151-1157.

Löning T, Meichsner M, Milde-Langosch K, et al. HPV DNA detection in tumours of the head and neck: a comparative light microscopy and DNA hybridization study. ORL J Otorhinolaryngol Relat Spec. 1987;49(5):259-269.

Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papil lomav irus- posit ive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261-269.

Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007;121(8):1813-1820.

Bussu F, Sali M, Gallus R, et al. HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker? Br J Cancer. 2013;108(5):1157-1162.

Rietbergen MM, Snijders PJ, Beekzada D, et al. Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas. Int J Cancer. 2014;134(10):2366-2372.

Morshed K, Polz-Dacewicz M, Rajtar B, Szymański M, Ziaja-Sołtys M, Gołabek W. The prevalence of E6/E7 HPV type 16 in laryngeal cancer and in normal mucosa. Pol Merkur Lekarski. 2005;19(111):291-293.

D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956.

Frisch M, Biggar RJ. Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas. Lancet. 1999;354(9188):1442-1443.

Hemminki K, Dong C, Frisch M. Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. Eur J Cancer Prev. 2000;9(6):433-437.

Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(6):622-635.

SahebJamee M, Boorghani M, Ghaffari SR, AtarbashiMoghadam F, Keyhani A. Human papillomavirus in saliva of patients with oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal. 2009;14(10):e525-e528.

Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35.

Huang SH, Perez-Ordonez B, Liu FF, et al. Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82(1):276-283.

Goldenberg D, Begum S, Westra WH, et al. Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck. 2008;30(7):898-903.

Lim MY, Dahlstrom KR, Sturgis EM, Li G. Human papillomavirus integration pattern and demographic, clinical, and survival characteristics of patients with oropharyngeal squamous cell carcinoma. Head Neck. 2016;38(8):1139-1144.

Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol. 2012;6(suppl 1):S16-S24.