Systematic Review and Meta-Analysis of Post-Treatment PET/CT in HPV-Associated Oropharyngeal Cancer

Abstract

Objective: To perform a systematic review with meta-analysis to investigate the utility of post-treatment PET/CT specifically in HPV-associated oropharyngeal squamous cell carcinoma following curative intent treatment. Methods: Random-effects meta-analysis was used to pool data from 7 observational studies (2013-2019) obtained from a database search of PubMed, Web of Science, and EMBASE using an a priori protocol with dual independent evaluation for inclusion, risk of bias assessment for acceptable methodology, and extraction of data for analysis. PET/CT results, treatment failure, imaging and interventions subsequent to PET/CT findings, and efficacy of salvage therapy were extracted. Results: Of the 907 post-treatment scans, PET/CT results were largely negative (76.2%; 95% CI, 63.4-85.6) and least often positive (11.3%; 95% CI, 8.8-14.4). PET/CT results were equivocal for 22.5% (95% CI, 12.5-36.9) and equivocal/positive for 34.2% of patients (95% CI, 25.1-44.5). Patients with an initial positive scan had the highest treatment failure rates (43.1%; 95% CI, 21.4-67.7) and those with an initial negative scan had the lowest rates (7.4%; 95% CI, 5.7-9.7). The equivocal and equivocal/positive scans had intermediate prevalence of 16.5% (95% CI, 9.4-27.6) and 16.7% (95% CI, 9.1-28.7), respectively. Conclusion: The low treatment failure rate following a negative PET/CT scan is reassuring, but the data are consistent with treatment failure rates up to 9.7% suggesting follow-up of these patients is prudent. Additionally, the low positive predictive value for treatment failure observed alludes to use of post-treatment PET/CT in HPV-associated disease frequently leading to unnecessary subsequent imaging and intervention.

Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI

“…21 A recent meta-analysis highlighted that PET-CT results were equivocal for 22.5% (95% CI, 12.5-36.9) and equivocal/positive for 34.2% of patients (95% CI, 25.1-44.5). 22 Recently, researchers and clinicians have begun to evaluate the clinical utility of ctHPVDNA and TTMV-HPVDNA in biological fluids for the diagnosis and monitoring of patients with HPV-positive cancers. 17,[23][24][25][26][27] Tumor progression is associated with the expression of oncogenic viral DNA and proteins.…”

Post‐treatment 18F‐fludeoxyglocuse‐positron emission tomography in human papillomavirus‐associated oropharyngeal cancer

“…Similarly, they identify a low positive-predictive value of only 43.0% in HPVassociated disease. 18 The differences between groups reported within this study, may reflect survival and treatment advantages inherent to HPV-associated OPSCC. Lower treatment failure and recurrence rates serve to reduce pre-test probability of events which impact on the performance characteristics of post-treatment PET imaging.…”

“…Conversely, the recognition of a lower positive predictive value in the context of HPV-associated OPSCC may potentially lead clinicians to form biases that delay investigation of positive and equivocal results and delay confirmation of recurrence which still occurs in 10%-15% of patients, with some studies reporting rates of as high as 25%. 18,20 Despite these drawbacks, PET imaging exhibits a relatively high specificity and negative predictive value. This means that clinicians can take reassurance in negative post-treatment PET results.…”

“…The authors reported both decreased sensitivity and specificity in post‐treatment PET when comparing HPV‐associated and non‐associated populations. Similarly, they identify a low positive‐predictive value of only 43.0% in HPV‐associated disease 18 …”

“…This adds increased cost and burden to the health system and patients alike. Conversely, the recognition of a lower positive predictive value in the context of HPV‐associated OPSCC may potentially lead clinicians to form biases that delay investigation of positive and equivocal results and delay confirmation of recurrence which still occurs in 10%–15% of patients, with some studies reporting rates of as high as 25% 18,20 …”