title: Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.
abstract: The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Denmark. emilie.nyberg.garnaes@rh.regionh.dk.
authors.forename: Emilie
authors.initials: E
authors.lastname: Garnaes
authors.affiliation: Department of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frederiksen
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Department of Pathology, Roskilde Hospital, University of Copenhagen, Denmark.
authors.forename: Luise
authors.initials: L
authors.lastname: Andersen
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Therkildsen
authors.affiliation: Department of Pathology, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Franzmann
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
authors.forename: Elo
authors.initials: E
authors.lastname: Andersen
authors.affiliation: Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Norrild
authors.affiliation: Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center and Department of Gynaecology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000378:metabolism / Q000821:virology*; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D014067:Tonsillar Neoplasms / Q000378:metabolism / Q000401:mortality / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: HPV; base of the tongue cancer; p16; survival; tonsillar cancer