Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Psychosocial Impact of Cancer Care Disruptions in Women With Breast Cancer During the COVID-19 Pandemic.

Background: The COVID-19 pandemic caused significant disruptions in cancer care, and preliminary research suggests that these disruptions are associated with increased levels of psychosocial distress among cancer survivors. The purpose of this study was to offer a descriptive report of the psychosocial functioning, perceived risk and fear of cancer progression, and COVID-19 pandemic impact and experiences in a unique, high-risk patient cohort: breast cancer survivors whose cancer treatment was delayed and/or changed due to the COVID-19 pandemic. Methods: This cross-sectional study included 50 women with dual carcinoma in situ, lobular carcinoma in situ, or invasive breast cancer whose cancer surgery was postponed due to the pandemic. As they awaited delayed surgery or shortly after they received delayed surgery, participants completed questionnaires on psychosocial functioning (depression, anxiety, sleep, and quality of life), their perceived risk and fear of cancer progression, patient-provider communication about disruptions in their care, personal impact of the pandemic, worry/threat about COVID-19, and COVID-19 symptoms/diagnoses. Descriptive statistics and bivariate correlations were computed among continuous study variables. Independent samples t-tests explored group differences in psychosocial functioning between survivors who were still awaiting delayed surgery and those who had recently received it. Results: Overall, the sample denied that the pandemic seriously negatively impacted their finances or resource access and reported low-to-moderate levels of psychosocial distress and fear about COVID-19. Twenty-six percent had clinically significant levels of fear of cancer progression, with levels comparable to other recent work. About a third were still awaiting delayed cancer surgery and this group reported lower satisfaction with communication from oncology providers but overall did not seem to report more psychosocial difficulties than those who already had surgery. Conclusion: Shortly before or after primary breast cancer surgery that was delayed due to the COVID-19 pandemic, this sample of survivors appears to be generally managing well psychosocially. However, many psychosocial difficulties (e.g., fear of cancer recurrence/progression) typically have an onset after the completion of treatment, therefore, research should continue to follow this cohort of cancer survivors as the pandemic's direct impact on their care likely increases their risk for these difficulties later in survivorship.