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The role of human papillomavirus in p16‐positive oral cancers
Author(s) -
Belobrov Simone,
Cornall Alyssa M.,
Young Richard J.,
Koo Kendrick,
Angel Christopher,
Wiesenfeld David,
Rischin Danny,
Garland Suzanne M.,
McCullough Michael
Publication year - 2018
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12649
Subject(s) - in situ hybridization , immunohistochemistry , chromogenic in situ hybridization , hpv infection , genotyping , human papillomavirus , biology , laser capture microdissection , polymerase chain reaction , papillomaviridae , virology , pathology , cancer research , medicine , cancer , messenger rna , gene , genotype , cervical cancer , gene expression , biochemistry , genetics
Background The aim of this study was to identify the presence and frequency of human papillomavirus ( HPV ) nucleic acid in p16‐positive oral squamous cell carcinomas ( OSCC s), to assess whether the virus was transcriptionally active and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC . Methods Forty‐six OSCC patients treated between 2007 and 2011 with available formalin‐fixed paraffin‐embedded ( FFPE ) specimens were included. Twenty‐three patients were positive for p16 by immunohistochemistry ( IHC ) and these were matched with 23 patients with p16‐negative tumours. Laser capture microdissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high‐risk HPV types using a PCR ‐ ELISA method based on the L1 SPF 10 consensus primers, and a real‐time PCR method targeting HPV ‐16 and HPV ‐18 E6 region. Genotyping of HPV ‐positive cases was performed using a reverse line blot hybridization assay (Inno‐LiPA). RNAScope ® (a chromogenic RNA in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high‐risk HPV types for detection of transcriptionally active virus. Results HPV DNA was found in 3 OSCC cases, all of which were p16 IHC ‐positive. Two cases were genotyped as HPV ‐16 and one as HPV ‐33. Only one of the HPV ‐16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH . Conclusion We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non‐viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC .