Prognostic and predictive values of baseline and mid-treatment FDG-PET in oropharyngeal carcinoma treated with primary definitive (chemo)radiation and impact of HPV status : review of current literature and emerging roles

Background and purpose: This study provides a review of the literature assessing whether semiquantitative PET parameters acquired at baseline and/or during definitive (chemo)radiotherapy ("prePET" and "iPET") can predict survival outcomes in patients with oropharyngeal squamous cell carcinoma (OPC), and the impact of human papilloma virus (HPV) status. Material and methods: A literature search was carried out using PubMed and Embase between 2001 to 2021 in accordance with PRISMA. Results: The analysis included 22 FDG-PET/CT studies [1-22], 19 pre-PET and 3 both pre-PET and iPET, The analysis involved 2646 patients, of which 1483 are HPV-positive (17 studies: 10 mixed and 7 HPV-positive only), 589 are HPV-negative, and 574 have unknown HPV status. Eighteen studies found significant correlations of survival outcomes with pre-PET parameters, most commonly primary or "Total" (combined primary and nodal) metabolic tumour volume and/or total lesional glycolysis. Two studies could not establish significant correlations and both employed SUVmax only. Two studies also could not establish significant correlations when taking into account of the HPV-positive population only. Because of the heterogeneity and lack of standardized methodology, no conclusions on optimal cut-off values can be drawn. Ten studies specifically evaluated HPV-positive patients: five showed positive correlation of pre-PET parameters and survival outcomes, but four of these studies did not include advanced T or N staging in multivariate analysis, and two studies only showed positive correlations after excluding high risk patients with smoking history or adverse CT features. Two studies found that prePET parameters predicted treatment outcomes only in HPV-negative but not HPV-positive patients. Two studies found that iPET parameters could predict outcomes in HPV-positive patients but not prePET parameters. Conclusion: The current literature supports high pre-treatment metabolic burden prior to definitive (chemo)radiotherapy can predict poor treatment outcomes for HPV-negative OPC patients. Evidence is conflicting and currently does not support correlation in HPV-positive patients.