Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy

Abstract

Background: Human papilloma virus (HPV) infection, p16 expression and hypoxia may play important roles in the carcinogenesis, treatment response and toxicities of head and neck squamous cell carcinoma (HNSCC). The aim of this analysis was to assess whether there is any correlation between pre-radiotherapy (RT) anemia, p16 expression and toxicities and local control for patients undergoing definitive therapy. Methods: 79 HNSCC patients who had undergone radiochemotherapy (RCT) or RT-antibody therapy were retrospectively analyzed. p16 (INK4A) expression was detected by immunohistochemical analysis. Factors predisposing for acute side effects were examined by uni- and multivariate analysis. Results: p16 overexpression was detected in 32 cases. Pretreatment anemia was present in one third of patients. Only 5% of patients were characterized by both pre-RT anemia and p16 overexpression. p16 expression was significantly associated with acute grade 3 toxicity. 47% of p16-positive patients developed grade ≥ 3 radiodermatitis compared to 26% of p16-negative patients (p = 0.04). A reduced risk of severe skin toxicities was noted for patients with hypoxic blood values before RT. p16 expression was significantly correlated with local control (p = 0.002). Conclusions: p16 expression is associated with better response to definitive combined treatment (RCT, RT + cetuximab), but also significantly related to acute high-grade toxicity.

Investigation of p16 status, chemotherapy regimen, and other nutrition markers for predicting gastrostomy in patients with head and neck cancer

“…This subset of patients is likely to be those undergoing unilateral radiotherapy treatment and, therefore, not identified as a high‐risk patient who receives bilateral treatment. This finding of positive p16 status increasing the need for proactive gastrostomy may be explained by other studies that have reported that patients with p16‐positive disease have higher acute toxicity than p16‐negative disease, and rates of dysphagia and organ toxicity are higher in patients with p16‐positive disease . We also found that current smoking status had an association with the need for a proactive gastrostomy, which is in line with other studies .…”

Polymorphism of regulatory region of APEH gene (c.-521G>C, rs4855883) as a relevant predictive factor for radiotherapy induced oral mucositis and overall survival in head neck cancer patients

“…Neither has it demonstrated OM progression to be correlated with hemoglobin level before RTH. Such correlation was found by Becker-Schiebe et al [ 36 ]. They confirmed that OM was observed less often in patients with pretreatment anemia, while p16 expression was significantly associated with severe OM [ 36 ].…”

Biological dose-escalated definitive radiation therapy in head and neck cancer

“…19,20 Survival and radiobiological studies are therefore needed, ideally, grouping tumour cases by factors that affect patient response to radiation such as: general health status, living habits, normal tissues and tumour biological parameters, tumour microenvironment features etc. [20][21][22][23] Doseresponse models on tumour response to radiation certainly need to be investigated more.…”