Minako Yokoyama

Utility of circulating human papillomavirus DNA as a biomarker for detection and prognosis of cervical cancer in Japanese patients

Cervical cancer (CC), the fourth most common cancer in women, is caused predominantly by human papillomavirus (HPV). Although measuring serum squamous cell carcinoma antigen (SCC Ag) can be useful for detecting recurrence of SCC, a major type of CC, its prognostic value remains unclear. This study focuses on the utility of circulating cell-free HPV (ccfHPV) DNA in plasma as a biomarker, with particular emphasis on its relevance to high-risk HPV subtypes prevalent in Japan. A prospective study of 26 CC patients and 23 females diagnosed with pre-cancerous lesions was conducted. Patients were selected carefully to include only those with single high-risk HPV subtypes (i.e., HPV16, 18, 52, or 58), reflecting regional HPV epidemiology. ccfHPV DNA was isolated from plasma and analyzed by droplet digital PCR targeting the HPV E7 genes. The detection rate of ccfHPV DNA in CC patients before clinical treatment was 57.7%. The detection rate correlated significantly with tumor size (r = 0.624, P < 0.01) and clinical stage (r = 0.844, P < 0.01). No ccfHPV DNA was detected in the females with pre-cancerous lesions. By contrast, of the 13 concurrent chemoradiotherapy cases, two relapsed within 6 months post-treatment. In those cases, ccfHPV DNA levels rose earlier than SCC Ag levels. The 11 CC cases in which no ccfHPV DNA was detected within 1 month post-treatment did not relapse. ccfHPV DNA is a useful biomarker for advanced-stage CC and for predicting prognosis, particularly in the Japanese clinical setting.