Open AccessTargeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV‐Positive Oropharyngeal Cancer
Author(s) -
Shen Sarek,
Saito Yuki,
Ren Shuling,
Liu Chao,
Guo Theresa,
Qualliotine Jesse,
Khan Zubair,
Sadat Sayed,
Califano Joseph A.
Publication year - 2020
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599820903031
Subject(s) - medicine , biomarker , oncology , odds ratio , receiver operating characteristic , confidence interval , cohort , area under the curve , retrospective cohort study , cancer , gastroenterology , logistic regression , biology , biochemistry
Objective The incidence and survivorship of human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance. We also assessed the assay’s applicability in screening for HPV+ OPSCC. Study Design Retrospective cohort study. Setting Two tertiary academic hospitals. Subjects and Methods Forty‐nine patients with posttreatment OPSCC were enrolled. Separately, 21 treatment‐naive patients and 40 controls were included in the screening analysis. Salivary rinses were obtained from these cohorts and biomarker levels were quantified. Receiver operative characteristic (ROC) curves and multivariate logistic models were used to assess performance of biomarker combinations. Results Eight patients (16.3%) in the posttreatment cohort developed locoregional recurrence. Recurrence was associated with alcohol use (odds ratio [OR], 6.12; 95% confidence interval [CI], 0.26‐3.79) and advanced nodal disease (OR, 2.21; 95% CI, 1.52‐3.01). A panel of HPV DNA and methylated EDNRB improved detection of recurrent disease (area under the curve [AUC], 0.88) compared to single markers (AUC, 0.69‐0.78). Positive biomarkers preceded clinical detection by 2.4 ± 1.6 months and was associated with nearly 40‐fold risk of recurrence (OR, 36.4; 95% CI, 1.15‐45.22). Within the screening analysis, single biomarkers demonstrated moderate sensitivity and specificity (AUC, 0.59‐0.83) in the detection of primary disease. A panel combining HPV DNA markers with methylated EDNRB and methylated PAX5 improved AUC to 0.93. Conclusion Detection of high‐risk HPV DNA or aberrant hypermethylation in oral rinses is associated with presence and recurrence of OPSCC. Targeting both markers in saliva may have utility in long‐term surveillance.