Use of Human Papillomavirus 16 (HPV16) Cell Free DNA for Assessment of Response to Chemoradiation in HPV-Associated Oropharyngeal Cancer

Abstract

much higher likelihood of cure. Several prognostic groupings have been proposed and we evaluate these in a large independent cohort. Materials/Methods: After institutional review board approval, an institutional database was queried for patients with HPV or p16 positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT), and 247 cases were identified. Patient, tumor, and treatment factors were abstracted from the charts. Tested groupings included the American Joint Committee on Cancer (AJCC) TNM staging system, the Radiation Therapy Oncology Group (RTOG) 0129 risk groups (Low Risk Z 10 pack years or >10 pack years with N0e2a, Intermediate Risk Z >10 pack years and N2be3), and the Princess Margaret Hospital (PMH) prognostic groups (I Z T1e3N0e2b, II Z T1e3N2c, III Z T4 or N3). Outcomes, including locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated from the end of RT and estimated via Kaplan-Meier method. Comparisons were made via log-rank test.Results: Median follow-up of patients alive at last contact was 24 months. All patients were treated with definitive RT alone (n Z 38, 15.4%) or concurrent chemotherapy and RT (n Z 209, 84.6%). For the entire cohort 2 year LRC was 94.6%, FFDM 92%, and OS 92.5%. AJCC stage was I in 4 patients (1.6%), II in 13 (5.3%), III in 35 (14.2%) or IVAeB in 195 (78.9%). AJCC stage was not prognostic for LRC (P Z .30), FFDM (P Z .90), or OS (P Z .31). Per RTOG risk groups, 170 were low risk (68.8%), and 77 were intermediate risk (31.2%). RTOG risk groups were not prognostic for LRC (P Z .94), FFDM (P Z .86), or OS (P Z .08). Per PMH prognostic groups, 180 were stage I (72.9%), 37 were stage II (15%), and 30 were stage III (12.1%). PMH prognostic groups were not significant for LRC (P Z .72), but were significant for FFDM (P Z .03) and OS (P Z .003). Actuarial OS at 2 years for PMH stage I was 94.8%, for stage II was 94.5%, and for stage III was 76.6%. Conclusion: Outcomes for patients with HPV-associated oropharyngeal cancer treated with definitive RT are excellent. The proposed PMH stage grouping resulted in improved survival prediction at 2 years compared with RTOG risk groups or AJCC TNM staging.

Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer

“…Similarly, plasma circulating tumor HPV16 DNA (ctHPV16DNA) is detectable in the majority of patients with HPV-associated OPSCC (12,(17)(18)(19)(20). Limited prior data have shown that ctHPV16DNA levels become largely undetectable after CRT in most patients, and that ctHPV16DNA levels may increase at the time of disease recurrence (12,(19)(20)(21). These prior studies retrospectively analyzed limited subsets of patients using real-time PCR.…”

Circulating HPV DNA in the Management of Oropharyngeal and Cervical Cancers: Current Knowledge and Future Perspectives

“…Blood-based biomarkers represent an ideal potential modality for the early detection or surveillance of HPV-associated cancers such as OPC and CEC. In the recent years ct-DNA has gained much attention as a method of investigating and monitoring tumor biology and clinical status [ 84 , 95 ]. Ongoing research is appraising the potential role of circulating HPV DNA in HPV-related cancers for this purpose.…”

“…Serum HPV DNA can be also be used to monitor for any residual disease after CRT [ 83 ]. Limited prior data has shown that HPV16 ct-DNA levels become largely undetectable post-CRT in most patients, and that HPV16 ct-DNA levels may increase at the time of disease recurrence [ 83 , 84 ]. Dynamic variations of serum HPV ct-DNA levels are associated with response to treatment of localized or metastatic HPV-related OPC [ 80 , 83 , 85 ].…”

The evolution of Epstein-Barr virus detection in nasopharyngeal carcinoma

“…However, several practical issues, including harmonization of the assay to measure cf HPV DNA, still need to be addressed prior to its clinical implementation. Nonetheless, few groups have reported an association between such a biomarker and advanced nodal status and overall TNM stage, with potential utility in clinical prognostication and monitoring of treatment response 24 , 25 .…”