It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta‐analysis

Abstract

The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16− were 269. The meta‐analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82–0.94) and 0.94 (95% CI: 0.85–0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9–32.1) and 0.05 (95% CI: 0.02–0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.

Accuracy of Salivary Circulating Tumor Human Papillomavirus DNA in Detecting Oropharyngeal Cancer

“…39 Finally, given interest in ctHPV DNA serving as a biomarker of early disease, the above analysis was repeated post hoc and compared between patients with localized (ie, stages 2 or 2) and advanced (ie, stages 3 or 4) tumors. [21][22][23][24][25] The generated SROC curves were plotted against one another on the same set of axes for qualitative comparison. Note that the study from Ahn et al 27 was excluded from these additional analyses due to its lack of available individuallevel patient data.…”

“…AUC values of 0.50, 0.70 to 0.80, 0.80 to 0.90, and above 0.90 were taken as the test conferring zero, acceptable, excellent, or outstanding predictive value, respectively, per literature recommendations . Finally, given interest in ctHPV DNA serving as a biomarker of early disease, the above analysis was repeated post hoc and compared between patients with localized (ie, stages 2 or 2) and advanced (ie, stages 3 or 4) tumors . The generated SROC curves were plotted against one another on the same set of axes for qualitative comparison.…”

“…[16][17][18][19][20] Studies have recently been extended to the HN cancer population, showing how plasma ctHPV DNA can accurately detect HPV-positive tumors before traditional diagnostics. [21][22][23][24][25] Importantly, these studies focused on samples isolated from blood despite other bodily fluids also containing ctHPV DNA.…”

Multimodal detection of molecular residual disease in high-risk locally advanced squamous cell carcinoma of the head and neck

“…Another dPCR assay (tumor tissue modified viral) has been validated in p16+ OPC in different cohorts [ 26 , 39 ] with pre-treatment sensitivity of 92.5% and negative predictive value (NPV) of 99.4% [ 25 ], but limited accuracy of MRD detection in the first 6 months post-CRT. A recent meta-analysis from several studies has shown a sensitivity of 91% for HPV DNA detection using different HPV genotypes including only plasma samples at diagnosis [ 40 ]. The sensitivity in our study at baseline was 100% for both HPV-seq and dPCR.…”