Abstract
Head and neck cancer treatment protocols still lack well-established biomarkers of prognostic and predictive value. It is well known that human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancers are distinct entities concerning tumor biology and clinical outcome. However, there is an ongoing debate whether tumor suppressor p16INK4 status alone or both p16INK4 and HPV detection should be used in clinical settings. The aim of this study was to investigate p16INK4-immunolabelled and HPV-induced rates and determine their clinical significance in 110 primary head and neck squamous cell carcinomas. The expression of p16INK4 protein was assessed with immunohistochemistry, while high-risk HPV detection was performed using DNA PCR method. P16INK4 immunolabelling was detected in 17.3% of all tumor samples, and in 38.1% of oropharyngeal malignancies. Oropharyngeal, p16INK4-immunolabelled tumors showed an improved disease-specific survival compared to the non-p16INK4-immunolabelled group (median survival: 30.3 vs. 8.8 months, p < 0.001 with the log-rank test). Furthermore, 56% of p16INK4-immunolabelled cases were tested positive for HPV-DNA. The HPV-induced group presented better disease-specific survival compared to the non-HPV-induced cases (median survival: 25.9 vs. 9.5 months, p = 0.024 with the log-rank test). Improved response rates to neoadjuvant chemotherapy were observed both in p16INK4-immunolabelled and p16INK4- immunolabelled/HPV DNA- containing groups (Fisher’s exact test: p = 0.025 and p = 0.009). In conclusion, p16INK4 immunohistochemistry proved to be a reliable and affordable tool for prognostic and predictive testing of head and neck squamous cell cancers. The p16INK4 immunopositivity status alone was confirmed to be an equally precise indicator of clinical outcome as p16INK4/HPV DNA PCR double testing.
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References
Ferlay J et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
Gillison ML et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709–720
Hashibe M et al (2007) Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the international head and neck cancer epidemiology consortium. J Natl Cancer Inst 99(10):777–789
Mehanna H et al (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer–systematic review and meta-analysis of trends by time and region. Head Neck 35(5):747–755
Kreimer AR et al (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev 14(2):467–475
Schache AG et al (2011) Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res 17(19):6262–6271
Vankos JB et al (2015) The prognostic role of expression of p16 tumor suppressor gene in Hungarian patients with oral squamous cell carcinoma. Magy Onkol 59(4):352–359
Lewis JS Jr, Chernock RD (2014) Human papillomavirus and Epstein Barr virus in head and neck carcinomas: suggestions for the new WHO classification. Head Neck Pathol 8(1):50–58
Chaturvedi AK et al (2013) Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol 31(36):4550–4559
Castellsague X et al (2016) HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst 108(6):djv403
Dreyer JH et al (2013) Detection of HPV infection in head and neck squamous cell carcinoma: a practical proposal. Virchows Arch 462(4):381–389
Jordan RC et al (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36(7):945–954
Fakhry C et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261–269
Ang KK et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35
O’Sullivan B et al (2013) Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol 31(5):543–550
Ng M et al (2014) Smoking prevalence and cigarette consumption in 187 countries, 1980–2012. JAMA 311(2):183–192
Cancer Genome Atlas Network (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This research was approved by the Semmelweis University’s Regional, Institutional Scientific and Research Ethics Committee (SE TUKEB 105/2014).
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L. Tamas and I. Petak contributed equally to this work.
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Brauswetter, D., Birtalan, E., Danos, K. et al. p16INK4 expression is of prognostic and predictive value in oropharyngeal cancers independent of human papillomavirus status: a Hungarian study. Eur Arch Otorhinolaryngol 274, 1959–1965 (2017). https://doi.org/10.1007/s00405-016-4412-8
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DOI: https://doi.org/10.1007/s00405-016-4412-8