Circulating HPV16 DNA in Blood Plasma as Prognosticator and Early Indicator of Cancer Recurrence in Radio-Chemotherapy for Anal Cancer

SIMPLE SUMMARY: Anal cancer, which is characterized by one of the highest human papillomavirus (HPV) positive case rates, is a rare disease accounting for only 0.5% of new cancer cases. Currently, there are no molecular markers for anal cancer. Circulating tumor–related HPV (ctHPV) in liquid biopsy as a substitute for conventional tumor biopsy offers great opportunities for survival prediction and molecular response assessment. Little is known about the ctHPV16 viral load in patients with anal cancer, its impact on survival, or its relationship to other clinical parameters. In this research we investigated the implication of ctHPV16 for monitoring treatment effects, disease relapse after treatment as well as impact on clinical outcome of anal cancer patients treated with definitive chemoradiation. We demonstrated the utility of detecting HPV status in addition to SUVmax and N, allowing for better stratification of the patient for therapy. ABSTRACT: Background: Implementation of anal squamous cell carcinoma (ASCC) treatment modifications requires reliable patient risk stratification. The circulating tumor–related human papillomavirus type 16 (ctHPV16) may play a role in predicting survival or assessing treatment response. Methods: The study included 62 ASCC patients treated with chemoradiotherapy. A threshold of 2.5 was used to determine the maximum standardized uptake value (SUVmax). The ctHPV16 viral load (VL) was quantified by qPCR. Results: In the multivariate Cox analysis, lower SUVmax (p = 0.047) and ctHPV16–positive (p = 0.054) proved to be independent prognostic factors for favorable overall survival (OS). In the subgroup with the higher SUVmax, ctHPV16 and nodal (N) status were independent prognostic factors with p = 0.022 for ctHPV16 and p = 0.053 for N. The best survival rate (95%) presented ctHPV16–positive/N–negative patients. High ctHPV16 VL tended to be slightly specific for patients younger than 63 years (p = 0.152). The decrease in ctHPV16 VL to undetectable level after the end of treatment correlated with the overall clinical response. Conclusions: A prognostic stratification by SUVmax, ctHPV16 and N–positive status allows consideration of more aggressive treatment in high–risk patients (those with high SUVmax, ctHPV16–negative, and N–positive) or de–intensification of therapy in low–risk patients (those with low SUVmax, ctHPV16–positive and N–negative). However, prospective clinical trials on a large group are needed.