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

Rettig, Eleni M.; Wentz, Alicia; Posner, Marshall R.; Gross, Neil D.; Haddad, Robert I.; Gillison, Maura L.; Fakhry, Carole; Quon, Harry; Sikora, Andrew G.; Stott, William; Lorch, Jochen H.; Gourin, Christine G.; Guo, Yingshi; Xiao, Weihong; Miles, Brett A.; Richmon, Jeremy D.; Andersen, Peter E.; Misiukiewicz, Krzysztof; Chung, Christine H.; Gerber, Jennifer E.; Rajan, Shirani D.; D’Souza, Gypsyamber

doi:10.1001/jamaoncol.2015.2524

Cited by 86 publications

(70 citation statements)

References 25 publications

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“…Following treatment, HPV-driven oropharyngeal cancer (HPV-OPC) has good survival, with a 5-year survival rate of 82% [2–4]. While recurrence risk remains low among HPV-OPC [5–7], current standard of care surveillance includes intensive posttherapy monitoring that could include physical exam, fiberoptic examinations, and radiologic imaging procedures. These procedures are associated with significant time, resources, and additional costs.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

et al. 2017

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Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95%CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

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Section: Introductionmentioning

confidence: 99%

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

et al. 2017

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“…Most data on the role of viral cfDNA as a prognostic marker comes from studies reporting DNA of EpsteinBarr virus (EBV) in patients who underwent treatment due to nasopharyngeal carcinoma (NPC). Circulating EBV DNA has been tested as a marker for NPC since 1998 [18,19] and correlates positively with disease stage and exhibits prognostic value in patients with NPC [20]. The drop in viral DNA in the blood during RT/CHRT was accompanied by remission of NPC as a response to treatment [21].…”

Section: Discussionmentioning

confidence: 99%

Post-Treatment Circulating Free HPV DNA As a Marker of Treatment Outcome in Patients with HPV-Related Propharyngeal Cancer After Radio(chemo)therapy

Tw¹,

Mazurek²,

Ånietura³

et al. 2017

Cell Mol Med

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Circulating cell-free HPV16 DNA (cfHPV DNA) assessed after treatment completion was tested as a prognostic marker of treatment failure in patients with HPVrelated oropharyngeal cancer (OPC) treated with radiotherapy alone (RT) or radiotherapy combined with chemotherapy (CHRT). Fifty-five patients with OPC in whom cfHPV DNA was found prior to RT/CHRT were included into the study. cfHPV DNA was subsequently assessed after treatment completion. cfHPV DNA remission (cfHPVrem) was defined as the absence of cfHPV DNA after treatment completion. The association between cfHPVrem and the risk of local, nodal or distant failure was calculated. Survival curves were calculated according to the Kaplan-Meier technique and compared according to cfHPVrem after treatment completion with the log-rank test. Thirteen (24%) patients presented no cfHPVrem after treatment completion. For these patients, the risk of nodal failure was significantly higher (HR=9.38, 95% CI: 1.63-53.97, p=0.009) than for patients with cfHPVrem. The probability of dissemination was comparable in patients with cfHPVrem and with no cfHPVrem (p=0.95). For patients with HPV related OPC, who has no cfHPVrem after RT/CHRT completion stricter follow up is proposed due to higher risk of nodal failure.

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“…Patients with a prevalent diagnosis of oropharyngeal cancer were eligible. Participants at JHH included people diagnosed with HPV-OPC from 2009 to 2013 who were in follow-up as part of a different study[11] and were recruited to participate in this study (80% of those asked agreed). Participants approached for enrollment at GBMC were patients undergoing routine clinical surveillance (70% of patients approached agreed to participate).…”

Section: Methodsmentioning

confidence: 99%

Patient experience and anxiety during and after treatment for an HPV-related oropharyngeal cancer

et al. 2016

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Objectives Diagnosis with an HPV-related oropharyngeal cancer includes unique social issues. However, it is unknown how common these psychosocial issues are for patients and whether they continue after treatment. Materials and Methods Patients with pathologically confirmed HPV-positive oropharyngeal cancer (HPV-OPC, n=48) were recruited from two medical centers. Participants completed a computer assisted self interview that explored their psychosocial experiences during and after treatment. We examined responses overall and by age. Results The majority of participants with confirmed HPV-OPC, reported being told that HPV could have (90%) or did cause (77%) their malignancy, but only 52% believed that HPV was the main cause of their OPC. Participants over 65 years were less likely than younger participants to report that their doctors told them their tumor was HPV-positive (50% vs 84%, p=0.03). Anxiety that their tumor was HPV-related was a major issue among participants when first diagnosed (93%). However, only 17% still reported anxiety after treatment was complete. While many patients reported that providers discussed the emotional effects of diagnosis and treatment adequately (58%), almost half reported discussing these emotional effects inadequately (24%), or not at all (18%). Further, 18% reported that their families still wondered about some questions that they had never asked. Conclusion After treatment, some HPV-OPC patients remain concerned about HPV and have unanswered questions about HPV. Older patients had lower awareness of the role of HPV in their cancer.

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

Cited by 86 publications

References 25 publications

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

Post-Treatment Circulating Free HPV DNA As a Marker of Treatment Outcome in Patients with HPV-Related Propharyngeal Cancer After Radio(chemo)therapy

Patient experience and anxiety during and after treatment for an HPV-related oropharyngeal cancer

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