Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma

Abstract

Background:Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying ‘true’ residual disease.Methods:We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT).Results:In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer.Conclusions:We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.

Circulating human papillomavirus DNA as a surveillance tool in head and neck squamous cell carcinoma: A systematic review and meta‐analysis

“…The initial literature search yielded a total of 615 records from which 73 articles were selected for full‐text assessment (Figure ). After full‐text screening, 5 studies were eligible for inclusion (n = 600) (Figure and Table ) . In the pooled analysis of studies with demographic information (n = 488), patients had a median age of 60 years (range 25‐89 years) and the majority were male (n = 419, 86%) .…”

“…In the pooled analysis of studies with demographic information (n = 488), patients had a median age of 60 years (range 25‐89 years) and the majority were male (n = 419, 86%) . Four studies (n = 512) had patients from the United States, and one study had patients (n = 88) from Europe . All of the studies are conducted in countries with a high HPV prevalence …”

“…Only Dahlstrom et al specifically included patients with OPSCCs. This inclusion is in contrast to the remaining studies in which a more heterogeneous patient population was included . In addition to patients with OPSCCs (500/600, 83%), patients with oral cavity cancers (56/600, 9.3%), hypopharyngeal cancers (14/600, 2.3%), laryngeal cancers (21/600, 3.5%), cutaneous squamous cell carcinomas (3/600, 0.5%) as well as patients with an unknown cancer location (6/600, 1%) were included.…”

“…Of all the included patients, 52% (312/600) had cancers that were HPV+. The prevalence of HPV+ cancers varied between 32% ‐ 87% …”

“…The specific genomic location chosen for the primer design for the various PCR methods used also varied between studies. The majority of studies chose to design primers that were specific for the E6 and E7 region of HPV16 . In the study by Cao et al they additionally used primers targeting E6, E7 and the L1 region from HPV18.…”