Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI.

First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.

Campo F ，Paolini F ，Manciocco V ，Moretto S ，Pichi B ，Moretti C ，Blandino G ，De Pascale V ，Benevolo M ，Pimpinelli F ，Vidiri A ，Marzi S ，Ruggiero S ，Terrenato I ，Iocca O ，Venuti A ，Pellini R ... -  《-》

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer.

Chera BS ，Kumar S ，Shen C ，Amdur R ，Dagan R ，Green R ，Goldman E ，Weiss J ，Grilley-Olson J ，Patel S ，Zanation A ，Hackman T ，Blumberg J ，Patel S ，Thorp B ，Weissler M ，Yarbrough W ，Sheets N ，Mendenhall W ，Tan XM ，Gupta GP ... -  《-》

Preoperative Circulating Tumor HPV DNA and Oropharyngeal Squamous Cell Disease.

Lam D ，Sangal NR ，Aggarwal A ，Rajasekaran K ，Cannady SB ，Basu D ，Chalian A ，Weinstein G ，Brody RM ... -  《-》

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

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.

Paolini F ，Campo F ，Iocca O ，Manciocco V ，De Virgilio A ，De Pascale V ，Moretto S ，Dalfino G ，Vidiri A ，Blandino G ，Pimpinelli F ，Venuti A ，Pellini R ... -  《-》

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection. POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. We found that ctHPVDNA levels 1 day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.

O'Boyle CJ ，Siravegna G ，Varmeh S ，Queenan N ，Michel A ，Pang KCS ，Stein J ，Thierauf JC ，Sadow PM ，Faquin WC ，Wang W ，Deschler DG ，Emerick KS ，Varvares MA ，Park JC ，Clark JR ，Chan AW ，Busse PM ，Corcoran RB ，Wirth LJ ，Lin DT ，Iafrate AJ ，Richmon JD ，Faden DL ... -  《-》