The following is a summary of “Association of Pretreatment Circulating Tumor Tissue–Modified Viral HPV DNA With Clinicopathologic Factors in HPV-Positive Oropharyngeal Cancer” published in the October 2022 issue of Otolaryngol Head Neck Surgery by Rettig et al.

A dynamic, clinically meaningful biomarker for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma is circulating tumor tissue-modified viral (TTMV) HPV Deoxyribonucleic acid (DNA). Researchers didn’t know why there was such a big variation in pretreatment results from patient to patient. The purpose of the study was to define the clinicopathologic features of TTMV HPV DNA. Patients with HPV-positive oropharyngeal squamous cell carcinoma who were being treated with the hope of a complete recovery were included in this cross-sectional study conducted at the Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022. Exposures Demographic factors, tumor, and nodal staging, HPV genotype, and imaging findings are all part of the clinicopathologic profile. Using a digital droplet polymerase chain reaction-based assay, the presence or absence of circulating TTMV HPV DNA from any of the 5 genotypes (16, 18, 31, 33, and 35) were categorized as either detectable (40 fragments/mL) or undetectable (40 fragments/mL) prior to therapy.

There were 110 total patients, with a mean standard deviation (SD) age of 62.2 (9.4) years; 87% were male; 95% were White; and the mean (SD) race was White. With a median interquartile range(IQR) score of 315 (47-2686) fragments/mL (range, 0-60 061 fragments/mL), circulating TTMV HPV DNA was identified in 98 patients (89%). To date, 86 individuals (or 88% of the total) have been found to have TTMV HPV DNA of genotype 16, while 12 patients (12% of the total) had TTMV HPV DNA of genotypes other than 16. Clinical N stage was the strongest predictor of detecting TTMV HPV DNA in circulation. Only 4 of the 11 patients with clinical stage N0 disease (36% ) had detectable DNA, while 95% of the 99 patients with clinical stage N1 to N3 disease had DNA (percentage difference, 59%; 95% CI, 30%-87%). A majority of patients (7 of 12; 58%) with undetectable TTMV HPV DNA also had clinical stage N0 illness. 

With increasing clinical nodal stage, biggest lymph node diameter, and nodal maximum standardized uptake value on positron emission tomography/computed tomography, the prevalence and score of TTMV HPV DNA also rose. In multivariate analysis, TTMV HPV DNA score was substantially related to clinical nodal stage and nodal maximal standardized uptake value. 27 of the patients who had surgical intervention contained detectable TTMV HPV DNA, with those with lymphovascular invasion having a higher prevalence (12 of 12 [100%] vs. 9 of 15 [60%]). Nodal illness upon diagnosis of HPV-positive OPSCC was strongly linked with circulating TTMV HPV DNA in this cross-sectional investigation. It appears that assay sensitivity for diagnostic purposes may be poorer among patients without cervical lymphadenopathy, given the few patients with undetectable levels had largely clinical stage N0 illness. More research is needed to understand the mechanisms underlying this connection and the use of this biomarker for monitoring patients with undetectable baseline values.