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Human papillomavirus DNA load and p16 INK4a expression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy
Author(s) -
Rödel Franz,
Wieland Ulrike,
Fraunholz Ingeborg,
Kitz Julia,
RaveFränk Margret,
Wolff Hendrik A.,
Weiss Christian,
Wirtz Ralph,
Balermpas Panagiotis,
Fokas Emmanouil,
Rödel Claus
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28979
Subject(s) - anal cancer , anal carcinoma , oncology , immunohistochemistry , medicine , univariate analysis , chemoradiotherapy , viral load , cancer , dna , multivariate analysis , cancer research , pathology , biology , immunology , virus , genetics
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 load ≤ median 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.