title: p16INK4expression is of prognostic and predictive value in oropharyngeal cancers independent of human papillomavirus status: a Hungarian study.
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 p16INK4status alone or both p16INK4and 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 p16INK4protein was assessed with immunohistochemistry, while high-risk HPV detection was performed using DNA PCR method. P16INK4immunolabelling 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, p16INK4immunohistochemistry proved to be a reliable and affordable tool for prognostic and predictive testing of head and neck squamous cell cancers. The p16INK4immunopositivity status alone was confirmed to be an equally precise indicator of clinical outcome as p16INK4/HPV DNA PCR double testing.
authors.affiliation: MTA-SE Pathobiochemistry Research Group, Tűzoltó utca 37-47, Budapest, 1094, Hungary. brauswetter.diana@med.semmelweis-univ.hu.
authors.forename: Diana
authors.identifier: http://orcid.org/0000-0003-4199-282X
authors.initials: D
authors.lastname: Brauswetter
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, Szigony Str. 36, Budapest, 1083, Hungary.
authors.forename: Ede
authors.initials: E
authors.lastname: Birtalan
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, Szigony Str. 36, Budapest, 1083, Hungary.
authors.forename: Kornel
authors.initials: K
authors.lastname: Danos
authors.affiliation: NEUMANN Diagnostics Kft., Nagyvárad Str. 15, Pécs, 7623, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Kocsis
authors.affiliation: Department of Pathology and Experimental Cancer Research, Semmelweis University and MTA-SE Tumorprogression Research Group, Üllői Str. 26, Budapest, 1085, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenacs
authors.affiliation: Department of Pathology, Semmelweis University, Üllői Str. 93, Budapest, 1091, Hungary.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Timar
authors.affiliation: Faculty of Medicine, Semmelweis University, Üllői Str. 26, Budapest, 1085, Hungary.
authors.forename: Reka
authors.initials: R
authors.lastname: Mihalyi
authors.affiliation: Faculty of Medicine, Semmelweis University, Üllői Str. 26, Budapest, 1085, Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Horcsik
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, Szigony Str. 36, Budapest, 1083, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Polony
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, Szigony Str. 36, Budapest, 1083, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tamas
authors.affiliation: MTA-SE Pathobiochemistry Research Group, Tűzoltó utca 37-47, Budapest, 1094, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Petak
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: HPV; Head and neck cancer; Oropharynx; Prognosis; p16