Detection of circulating tumor human papillomavirus DNA before diagnosis of HPV‐positive head and neck cancer

Abstract

Human papillomavirus (HPV), most commonly HPV16, causes a growing subset of head and neck squamous cell carcinomas (HNSCCs), including the overwhelming majority of oropharynx squamous cell carcinomas in many developed countries. Circulating biomarkers for HPV‐positive HNSCC may allow for earlier diagnosis, with potential to decrease morbidity and mortality. This case‐control study evaluated whether circulating tumor HPV DNA (ctHPVDNA) is detectable in prediagnostic plasma from individuals later diagnosed with HPV‐positive HNSCC. Cases were participants in a hospital‐based research biobank with archived plasma collected ≥6 months before HNSCC diagnosis, and available archival tumor tissue for HPV testing. Controls were biobank participants without cancer or HPV‐related diagnoses, matched 10:1 to cases by sex, race, age and year of plasma collection. HPV DNA was detected in plasma and tumor tissue using a previously validated digital droplet PCR‐based assay that quantifies tumor‐tissue‐modified viral (TTMV) HPV DNA. Twelve HNSCC patients with median age of 68.5 years (range, 51‐87 years) were included. Ten (83.3%) had HPV16 DNA‐positive tumors. ctHPV16DNA was detected in prediagnostic plasma from 3 of 10 (30%) patients with HPV16‐positive tumors, including 3 of 7 (43%) patients with HPV16‐positive oropharynx tumors. The timing of the plasma collection was 19, 34 and 43 months before cancer diagnosis. None of the 100 matched controls had detectable ctHPV16DNA. This is the first report that ctHPV16 DNA is detectable at least several years before diagnosis of HPV16‐positive HNSCC for a subset of patients. Further investigation of ctHPV16DNA as a biomarker for early diagnosis of HPV16‐positive HNSCC is warranted.

Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium

“…If such a biomarker could be identified, it could be measured at regular intervals among HPV16-E6 seropositive people to indicate when more invasive examination is warranted. Circulating tumor HPV DNA can have high sensitivity and specificity for detecting HPV-positive OPC at the time of diagnosis, 39 and a recent study supports feasibility in a prediagnostic setting, 40 but studies with larger numbers of prediagnostic samples from HPV-positive OPC cases are critically needed. A compelling analogy is Epstein-Barr virus DNA detection in plasma, which can facilitate early detection of nasopharyngeal cancer.…”

HPV and head and neck cancers: Towards early diagnosis and prevention

“…In a recent prospective study, it was reported that cfHPV DNA detection in plasma is specific biomarkers with high sensitivity, representing a useful non-invasive diagnostic approach to identify HPV-related HNSCCs [ 118 ]. In addition, it was reported in a case-control study that in a subset of patients, cfHPV16 DNA was detected 3 years before the clinical diagnosis of HPV16-related HNSCC [ 119 ].…”

The Promise of Circulating Tumor DNA in Head and Neck Cancer

“…Additionally, in the way cervical cancer possesses an identifiable precursor lesion for screening, nothing similarly has been described for OPSCC. However, in a retrospective case–control study, Rettig et al have shown that HPV ctDNA detection can occur several years prior to the diagnosis of HPV-positive OPSCC, suggesting HPV ctDNA positivity could serve as a surrogate precursor lesion [ 36 ]. Of the 10 patients with HPV-positive OPSCC enrolled, 3 had early detectable HPV ctDNA in plasma collected at a median time of 30.5 months prior to diagnosis.…”