TY - JOUR
T1 - Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV-Positive Oropharyngeal Cancer
AU - Shen, Sarek
AU - Saito, Yuki
AU - Ren, Shuling
AU - Liu, Chao
AU - Guo, Theresa
AU - Qualliotine, Jesse
AU - Khan, Zubair
AU - Sadat, Sayed
AU - Califano, Joseph A.
N1 - Publisher Copyright:
© American Academy of Otolaryngology–Head and Neck Surgery Foundation 2020.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - HPV
KW - epigenetics
KW - human papillomavirus
KW - oropharyngeal squamous cell carcinoma
KW - promoter hypermethylation
KW - recurrence
KW - saliva
KW - screening
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U2 - 10.1177/0194599820903031
DO - 10.1177/0194599820903031
M3 - Article
C2 - 32041482
AN - SCOPUS:85079725547
SN - 0194-5998
VL - 162
SP - 512
EP - 519
JO - Otolaryngology - Head and Neck Surgery (United States)
JF - Otolaryngology - Head and Neck Surgery (United States)
IS - 4
ER -