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  • Human papillomavirus DNA load and p16INK4a expression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy.

Human papillomavirus DNA load and p16INK4a expression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy.

International journal of cancer (2014-05-20)
Franz Rödel, Ulrike Wieland, Ingeborg Fraunholz, Julia Kitz, Margret Rave-Fränk, Hendrik A Wolff, Christian Weiss, Ralph Wirtz, Panagiotis Balermpas, Emmanouil Fokas, Claus Rödel
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 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.

MATERIALS
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Product Description

Mitomycin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, ≥98% (HPLC), potency: ≥970 μg per mg (USP XXIV), γ-irradiated, suitable for cell culture
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, ≥970 μg/mg (USP XXIV)
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, powder, contains NaCl as solubilizer