Circulating tumor-tissue modified HPV DNA analysis for molecular disease monitoring after chemoradiation for anal squamous cell carcinoma: a case report

Squamous cell carcinoma (SCC) of the anus typically arises after human papillomavirus (HPV) infection. We report on the use of molecular disease monitoring using a novel blood test measuring circulating tumor-tissue -modified HPV DNA in two patients with anal cancer. Two patients with anal SCC received concurrent chemotherapy and radiation therapy (chemoRT) with curative intent, one with a T2N0 anal margin squamous cell carcinoma with a history of AIDS, and one with a T3N0 anal squamous cell carcinoma and a history of concurrent prostate cancer. HPV genotyping at diagnosis confirmed the presence of HPV16 DNA in both cases. Circulating, tumor-tissue-modified HPV DNA (TTMV-HPV DNA) was measured in the peripheral blood utilizing digital PCR at baseline and in follow-up. Disease burden was assessed post-treatment with standard anoscopy, biopsy, and PET/CT. Plasma TTMV-HPV DNA levels were elevated at diagnosis, and decreased during and after chemoRT completion in both cases. During post treatment surveillance, TTMV-HPV DNA levels correlated with disease status including one case with progressive local recurrence within 2 months, and one case with 12 months of local control both confirmed by biopsy. These case studies present the first use of circulating tumor-tissue-modified HPV DNA as a biomarker for anal cancer. Further study of this blood test an adjunct to standard treatment and monitoring is warranted in HPV-positive anal cancer.