Universität zu Köln

Roedel, Franz, Wieland, Ulrike, Fraunholz, Ingeborg, Kitz, Julia, Rave-Fraenk, Margret, Wolff, Hendrik A., Weiss, Christian, Wirtz, Ralph, Balermpas, Panagiotis ORCID: 0000-0001-5261-6446, Fokas, Emmanouil and Roedel, Claus (2015). Human papillomavirus DNA load and p16(INK4a) expression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy. Int. J. Cancer, 136 (2). S. 278 - 289. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

As the detection rate of HPV-DNA in anal carcinoma commonly exceeds 90%, a comparison between sole HPV-positive and HPV-negative cancers with respect to treatment response following chemoradiotherapy (CRT) and long-term oncological outcome is challenging. Against this background, we aimed to assess HPV types and HPV DNA load in formalin-fixed paraffin-embedded tissue (FFPE) of 95 patients treated with standard CRT for anal cancer to correlate viral load (/> median) with local failure, distant metastases, cancer-specific (CSS) and overall survival (OS) rates. Various clinicopathologic parameters and the immunohistochemical marker p16(INK4a) were evaluated for any correlation with HPV16 DNA load and were included in uni- and multivariate analyses. The overall prevalence of HPV DNA was 95.8% with HPV16 monoinfection being the most commonly encountered HPV type (78.9%), followed by HPV16 and 31, 35, 39, 44, 58, 66 and 81 dual infection in 9 patients (9.5%). HPV16 DNA load was significantly associated with p16(INK4a) expression (p = 0.001). Patients with HPV16 DNA loadmedian and low p16(INK4a) expression showed significantly worse local control (HPV16 DNA load: univariate p = 0.023, multivariate p = 0.042; p16(INK4a): univariate p = 0.021), and OS (HPV16 DNA load: univariate p = 0.02, multivariate p = 0.03). Moreover, a combined HPV16 DNA load and p16(INK4a) variable revealed a significant correlation to decreased local failure, and increased CSS and OS (p = 0.019, p = 0.04 and p = 0.031). In conclusion, these data indicate that HPV16 DNA load and p16(INK4a) expression are significant prognostic factors for local tumor control and overall survival of patients with anal SCC following CRT. What's new? As the detection rate of HPV-DNA in anal carcinoma commonly exceeds 90%, comparing solely HPV-positive and HPV-negative cancers with respect to treatment response following chemoradiotherapy and long-term oncological outcome is challenging. Here, the authors demonstrate for the first time that low initial HPV16 DNA load and low/negative p16INK4a expression in pretreatment biopsies are significant risk factors for local failure and decreased overall survival in patients treated with standard chemoradiotherapy. The findings provide a rationale for the implementation of a standardized HPV molecular and immunohistochemical evaluation protocol in clinical trials in patients with anal carcinoma that may require alternative treatment strategies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Roedel, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieland, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Fraunholz, Ingeborg UNSPECIFIED UNSPECIFIED UNSPECIFIED Kitz, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Rave-Fraenk, Margret UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolff, Hendrik A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED Balermpas, Panagiotis UNSPECIFIED orcid.org/0000-0001-5261-6446 UNSPECIFIED Fokas, Emmanouil UNSPECIFIED UNSPECIFIED UNSPECIFIED Roedel, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414606
DOI:	10.1002/ijc.28979
Journal or Publication Title:	Int. J. Cancer
Volume:	136
Number:	2
Page Range:	S. 278 - 289
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIV-POSITIVE MEN; INTRAEPITHELIAL NEOPLASIA; PROGNOSTIC-SIGNIFICANCE; OROPHARYNGEAL CANCER; NECK-CANCER; HPV; HEAD; SURVIVAL; TRIAL; P16 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41460