Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Sep 1;149(9):812-819.
doi: 10.1001/jamaoto.2023.1730.

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Joseph Califano  1   2 , Andrew Yousef  1 , Heba Mostafa  3 , Alexandra Valsamakis  3   4 , Xinlian Zhang  5 , Nikolaos Batis  6 , Christy Varghese  6 , Joanna Parish  6 , Michael Forman  3 , Junko Jarrett  7 , Karen Messer  5 , Hisham Mehanna  6
Affiliations
Clinical Trial

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Joseph Califano et al. JAMA Otolaryngol Head Neck Surg. .

Erratum in

  • Errors in Table 2.
    [No authors listed] [No authors listed] JAMA Otolaryngol Head Neck Surg. 2024 Jun 1;150(6):530. doi: 10.1001/jamaoto.2024.0317. JAMA Otolaryngol Head Neck Surg. 2024. PMID: 38483368 Free PMC article. No abstract available.

Abstract

Importance: Head and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported.

Objective: To identify patients with low-risk HPVOPC at risk for recurrence by detection of HPV16 DNA in plasma and salivary rinses.

Design, setting, and participants: In this cohort study, 233 low-risk patients were recruited from 32 head and neck treatment centers in Ireland (1 [3.1%]), the Netherlands (1 [3.1%]), and the UK (30 [93.8%]) as part of the DE-ESCALATE HPV trial, an open-label, phase 3 randomized clinical trial examining treatment with cetuximab vs cisplatin for HPVOPC. Patients were assayed for the presence of HPV16 DNA in plasma and salivary rinse via a quantitative polymerase chain reaction-based assay.

Main outcomes and measures: Assay results were associated with risk of recurrence and lead time from HPV16 DNA detection to recurrence.

Results: Of 233 patients, 45 (19.3%) were women, and the mean (SD) age was 57.01 (8.45) years. A total 1040 salivary or blood samples were collected during the course of the study. With a median follow-up of 760 days, the sensitivity and specificity of combined plasma and salivary rinse HPV DNA assays for detecting recurrence were 65% and 87%, respectively. There was a median lead time of positive test to event/recurrence date of 19 days (range, 0-536 days) and mean (SD) of 122 (169.8) days.

Conclusion and relevance: The results of this cohort study suggest that in the setting of a randomized, prospective, phase 3 trial for low-risk patients with HPVOPC, posttreatment presence of HPV DNA in plasma and salivary rinses is associated with recurrence; a lead time between test positivity and clinical recurrence offers a potential opportunity for earlier detection of recurrence.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Califano reported a patent for a human papillomavirus biomarker pending from the University of California, San Diego. Dr Mostafa reported service on the advisory board of Seegene and a research contract with BioRad. Dr Valsamakis reported personal fees from Roche Diagnostic Solutions outside the submitted work. Dr Mehanna reported grants from Cancer Research UK, AstraZeneca, and GSK PLC; personal fees from Merck, MSD, Seagen, and Nanobiotix; shares and employment with Warwickshire Head Neck Clinic Ltd; and shares from Docspert outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Inclusion and Exclusion Criteria
Figure 2.
Figure 2.. Patients With a Recurrence or Persistence During the Study Period With Human Papillomavirus DNA Test Results
RT indicates radiotherapy.
Figure 3.
Figure 3.. Comparison of Recurrence-Free Probability in Patients With Positive vs Negative Human Papillomavirus (HPV) DNA Test Results
A, Either plasma or salivary rinse assays completed any time after treatment completion (HR, 33.19; 95% CI, 13.03-84.55). B, Plasma-alone assays completed any time after treatment completion (hazard ratio [HR], 13.15; 95% CI, 4.83-35.78). A univariate Cox regression shows significantly worse rates of recurrence in all groups with a positive assay. Because the HPV DNA test result is a time-varying predictor, a participant enters the risk set only after an assay is taken; thus, the risk set might change as time progresses.
See this image and copyright information in PMC

References

    1. Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus–positive head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3235-3242. doi:10.1200/JCO.2015.61.6995 - DOI - PMC - PubMed
    1. Mehanna H, Franklin N, Compton N, et al. . Geographic variation in human papillomavirus-related oropharyngeal cancer: data from 4 multinational randomized trials. Head Neck. 2016;38(1)(suppl 1):E1863-E1869. doi:10.1002/hed.24336 - DOI - PMC - PubMed
    1. Osazuwa-Peters N, Simpson MC, Massa ST, Adjei Boakye E, Antisdel JL, Varvares MA. 40-year incidence trends for oropharyngeal squamous cell carcinoma in the United States. Oral Oncol. 2017;74:90-97. doi:10.1016/j.oraloncology.2017.09.015 - DOI - PubMed
    1. Louie KS, Mehanna H, Sasieni P. Trends in head and neck cancers in England from 1995 to 2011 and projections up to 2025. Oral Oncol. 2015;51(4):341-348. doi:10.1016/j.oraloncology.2015.01.002 - DOI - PubMed
    1. Mehanna H, Beech T, Nicholson T, et al. . Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer–systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747-755. doi:10.1002/hed.22015 - DOI - PubMed

Publication types