Mooren, Jeroen J., Gultekin, Sibel E., Straetmans, Jos M. J. A. A., Haesevoets, Annick, Peutz-Kootstra, Carine J., Huebbers, Christian U., Dienes, Hans P., Wieland, Ulrike, Ramaekers, Frans C. S., Kremer, Bernd, Speel, Ernst-Jan M. and Klussmann, Jens P. (2014). P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias. Int. J. Cancer, 134 (9). S. 2108 - 2118. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16(INK4A) is often used as a surrogate marker for HPV-infection, although there is still controversy with respect its reliability. Our aim was to determine if P16(INK4A) overexpression can accurately predict both high-risk and low-risk-HPV-presence in (pre)malignant and benign head and neck lesions. P16(INK4A) immunohistochemistry was performed on paraffin-embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme-immunoassay and FISH analysis were used to assess HPV-presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16-positive, respectively. All tonsillar papillomas were HPV-negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or -11. P16(INK4A) immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16-positive and 5 out of 111 HPV-negative OPSCC (p<0.0001) and in all HPV16-positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV-status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic P16(INK4A) immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or -11-positive and HPV-negative benign and premalignant lesions of the tonsil and larynx, however, P16(INK4A) immunostaining is highly variable and cannot be recommended to predict HPV-presence.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mooren, Jeroen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gultekin, Sibel E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Straetmans, Jos M. J. A. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haesevoets, AnnickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peutz-Kootstra, Carine J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebbers, Christian U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dienes, Hans P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wieland, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramaekers, Frans C. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kremer, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speel, Ernst-Jan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klussmann, Jens P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-440351
DOI: 10.1002/ijc.28534
Journal or Publication Title: Int. J. Cancer
Volume: 134
Number: 9
Page Range: S. 2108 - 2118
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1097-0215
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IN-SITU HYBRIDIZATION; SQUAMOUS-CELL CARCINOMA; P16 PROTEIN; EXPRESSION; OVEREXPRESSION; DNA; INTEGRATION; LESIONS; P53; IDENTIFICATIONMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44035

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