Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma

Abstract

BackgroundHead and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression.MethodsA total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan–Meier analysis; the difference in survival was calculated with log rank test.ResultsA total of 21 male and 3 female with a mean age of 53.12 years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant.ConclusionThe result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not appear to be related to the expression of EGFR, Her-2-Neu, and GADD45 protein or presence of HPV. Bone involvement, perineural invasion, and GADD45 expression significantly predict OS and DFS. All patients who did not express Gadd45 died before 2 years. Study with more subjects and longer follow-up should be carried out to elucidate this relation further.

Immunohistochemical expression of epidermal growth factor receptor (EGFR) in South Asian head and neck squamous cell carcinoma: association with various risk factors and clinico-pathologic and prognostic parameters

“…Similar to our study, Srivastava et al also did not found a significant association of various risk factors with EGFR expression [ 19 ]. In contrast to our study, Panday et al, in a study involving 24 locally advanced HNSCC cases, did not found any significant association of EGFR expression with disease-free survival in patients taking neoadjuvant chemotherapy [ 20 ]. Similarly, Kumar et al suggested that EGFR expression did not predict response to neoadjuvant chemotherapy [ 21 ].…”

CMTM6 drives cisplatin resistance by regulating Wnt signaling through ENO-1/AKT/GSK3β axis

“…The treatment modalities of advanced OSCC are surgical removal of primary tumor followed by chemo-radiotherapy (3). However, neoadjuvant chemotherapy is commonly prescribed for surgically unresectable OSCC tumors that provide more surgical options (4). In spite of having all available treatment modalities, the 5-year survival rate of advanced tongue OSCC patients remains less than 50%, indicating towards resistance development against these therapies.…”

Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma

“…Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally, accounting for more than 95 % of head and neck cancers 1. With an annual new cases of more than 4,00,000 worldwide, two-thirds of the HNSCC cases are reported from developing countries, and only 40-50 % of the patients can reach five-year overall survival 2, 3. Unfortunately, the overall survival of patients with HNSCC has not been remarkably improved over the past 30 years, despite advances in traditional treatment for HNSCC, including surgery, radiotherapy and chemotherapy 4, 5.…”