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 paraffinembedded 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 5 0.001). Patients with HPV16 DNA load median and low p16 INK4a expression showed significantly worse local control (HPV16 DNA load: univariate p 5 0.023, multivariate p 5 0.042; p16 INK4a : univariate p 5 0.021), and OS (HPV16 DNA load: univariate p 5 0.02, multivariate p 5 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 5 0.019, p 5 0.04 and p 5 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.The majority of anal squamous cell carcinoma (SCC) is considered to originate from infection with human papilloma viruses (HPV). 1,2 Especially the role of high-risk oncogenic HPV types, most prominently HPV type 16 (HPV16), in the etiology of anal SCC is well established by a multitude of epidemiological and experimental investigations. 3,4 As a consequence, technologies for the detection of HPV DNA may constitute valuable screening tools for anal malignancies and are of important clinical relevance, especially after the development of a preventive vaccine for both men and women. 5 Depending on the method used, the prevalence of HPV DNA in anal carcinoma ranges from 75% to 100% with HPV16 (>75%) and less frequent HPV18 (<10%) detection in the majority of cases. 6,7 In clinical series of head and neck as well as cervical SCC, recent data indicate that treatment response to radiotherapy (RT) or chemoradiotherapy (CRT) is superior in HPV-positive tumors as compared with their HPV-negative counterparts. [8][9][10] An increased sensitivity of HPV-positive tumor cells towards irradiation and chemotherapeutic agents was also observed in vitro and in animal studies. [11][12][13] However, as the detection rate of HPV DNA in anal SCC commonly exceeds 90%, a comparison between sole HPV-positive and HPV-negative cancers with respect to treatment respon...

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RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder.

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Future studies should evaluate more effective prophylaxis protocols in CRT in order to reduce the high rates of nausea and emesis.