Simone Belobrov1, Alyssa M Cornall2,3,4, Richard J Young5, Kendrick Koo6, Christopher Angel7, David Wiesenfeld1,6,8, Danny Rischin9, Suzanne M Garland2,3,4, Michael McCullough1. 1. Melbourne Dental School, Faculty of Medicine Dentistry and Health Science, The University of Melbourne, Melbourne, VIC, Australia. 2. Regional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, VIC, Australia. 3. Murdoch Childrens Research Institute, Melbourne, VIC, Australia. 4. Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, VIC, Australia. 5. Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 6. Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia. 7. Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 8. Head and Neck Oncology Tumour Stream, Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia. 9. Divison of Cancer Medicine, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, VIC, Australia.
Abstract
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 (OSCCs), 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 SPF10 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.
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 (OSCCs), 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 SPF10 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.
Authors: Katalin Csurgay; Attila Zalatnai; Márta Benczik; Benedek Krisztián Csomó; Ferenc Horváth; Ádám Lőrincz; György Komlós; Zsolt Németh Journal: Pathol Oncol Res Date: 2021-12-22 Impact factor: 3.201
Authors: E Pérez-Islas; A García-Carrancá; E Acosta-Gio; N Reynoso-Noverón; H-A Maldonado-Martínez; M Guido-Jiménez; N Sobrevilla-Moreno; M Granados-García; W-B Pérez-Báez; D Vilar-Compte Journal: Med Oral Patol Oral Cir Bucal Date: 2022-03-01
Authors: Giuseppe Troiano; Agostino Guida; Gabriella Aquino; Gerardo Botti; Nunzia Simona Losito; Silvana Papagerakis; Maria Carmela Pedicillo; Franco Ionna; Francesco Longo; Monica Cantile; Antonio Pennella; Lucio Lo Russo; Giovanni Di Gioia; Maria Addolorata Mariggiò; Lorenzo Lo Muzio; Giuseppe Pannone Journal: Int J Mol Sci Date: 2018-09-08 Impact factor: 5.923
Authors: Kendrick Koo; Dmitri Mouradov; Christopher M Angel; Tim A Iseli; David Wiesenfeld; Michael J McCullough; Antony W Burgess; Oliver M Sieber Journal: Cancers (Basel) Date: 2021-03-01 Impact factor: 6.639