Abstract
BackgroundHuman papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HNSCC due to other risk factors. However, there is significant heterogeneity within HPV-associated HNSCC and 25% of these patients still do poorly despite receiving aggressive therapy. We currently have no good molecular tools to differentiate and exclude this “high-risk” sub-population and focus on “low-risk” patients for clinical trials. This has been a potential barrier to identifying successful de-escalation treatment strategies in HPV-associated HNSCC. We conducted an analysis of molecular markers with a well-known role in the pathogenesis of HPV-associated HNSCC and hypothesized that these markers could help independently predict recurrence and prognosis in these patients and therefore help identify at the molecular level “low-risk” patients suitable for de-escalation trials.MethodsWe analyzed 24 tumor specimens of patients with p16+ HNSCC who underwent definitive resection as primary treatment. Tissue microarray (TMA) was generated from the 24 pathology blocks and immunohistochemistry (IHC) was performed using highly specific antibodies for our chosen biomarkers (PI3K-PTEN, AKT pathway, mTOR, 4EBP1, S6, and pAMPK, ERCC-1). Transcriptome data was also obtained for 7 p16+ HNSCC patients from The Cancer Genome Atlas (TCGA). Data from the TMA and TCGA were analyzed for association of relapse-free survival (RFS) and overall survival (OS) with protein and gene expression of the chosen biomarkers.ResultsIncreased pAMPK protein activity by IHC and AMPK gene expression by TCGA gene expression data was correlated with improved RFS with a trend towards statistical significance.ConclusionsThis data suggests that increased pAMPK activity and expression may portend a better prognosis in HPV-associated HNSCC undergoing primary definitive resection. However, these findings require validation in larger studies.
Highlights
Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HNSCC due to other risk factors
In a multicenter cooperative group study, ECOG 1308, 80 patients with Stage III or IVA HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) received induction chemotherapy with three cycles of cisplatin, paclitaxel, and cetuximab followed by cetuximab combined with a lower dose of radiation therapy (RT), 54 Gy in 27 fractions, for those patients who achieved a clinical complete response to induction chemotherapy at the primary site
Much like ECOG 1308 all of these studies included a small number of patients and no definitive conclusion about this de-escalation strategy can be made without further data from larger studies
Summary
Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HNSCC due to other risk factors. We currently have no good molecular tools to differentiate and exclude this “high-risk” sub-population and focus on “low-risk” patients for clinical trials. This has been a potential barrier to identifying successful de-escalation treatment strategies in HPV-associated HNSCC. With the lower dose of radiation, the two-year progression-free survival (PFS) was 80% and two-year overall survival (OS) was 94% [9] These results are similar to those of the ECOG 2399 study, the Lancet Oncology study by Chen et al, and the OPTIMA study [10,11,12]. Much like ECOG 1308 all of these studies included a small number of patients and no definitive conclusion about this de-escalation strategy can be made without further data from larger studies
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