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Original Investigation |

Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus–Related Oropharyngeal Carcinoma

Eleni M. Rettig, MD1; Alicia Wentz, MA2; Marshall R. Posner, MD3; Neil D. Gross, MD4; Robert I. Haddad, MD5; Maura L. Gillison, MD, PhD6; Carole Fakhry, MD1,2; Harry Quon, MD7; Andrew G. Sikora, MD, PhD8; William J. Stott, CCRP9; Jochen H. Lorch, MD5; Christine G. Gourin, MD1; Yingshi Guo, MS6; Weihong Xiao, MD6; Brett A. Miles, DDS, MD10; Jeremy D. Richmon, MD1; Peter E. Andersen, MD9; Krzysztof J. Misiukiewicz, MD3; Christine H. Chung, MD1,11; Jennifer E. Gerber, MSc12 ; Shirani D. Rajan, MSPH13; Gypsyamber D’Souza, PhD2
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
3Tisch Cancer Institute, Head and Neck Oncology Center, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York
4Division of Surgery, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston
5Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
6Viral Oncology Program, Ohio State University Comprehensive Cancer Center, Columbus
7Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
8Department of Otolaryngology–Head and Neck Surgery, Baylor College of Medicine, Houston, Texas
9Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon
10Department of Otolaryngology, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York
11Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
12 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
13Louisiana State University School of Medicine, New Orleans
JAMA Oncol. 2015;1(7):907-915. doi:10.1001/jamaoncol.2015.2524.
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Importance  Human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear.

Objective  To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival.

Design, Setting, and Participants  Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study.

Main Outcomes and Measures  Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis.

Results  Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.

Conclusions and Relevance  Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

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Figure.
Survival by Detection of Persistent Human Papillomavirus Type 16 (HPV16) DNA in Pretreatment and Posttreatment Oral Rinse Samples

Persistent HPV 16 indicates detection of HPV16 DNA in oral rinses both at diagnosis and at any posttreatment visit.

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