Laryngopharyngeal Reflux and Laryngeal Squamous Cell Carcinoma

Background: Patients with squamous cell carcinoma (SCC) of the larynx are usually heavy smokers, and tobacco exposure has been clearly correlated with p53 tumor suppressor gene damages. In this prospective study we investigated the possible independent carcinogenic role of laryngopharyngeal reflux (LPR) by correlating the development of laryngeal SCC, with the presence of LPR and p53 alterations. Materials and Methods: Eighty-eight consecutive patients with laryngeal SCC treated at the ENT University Clinic of Florence preoperatively underwent a 24h dual-probe-pH-monitoring and laryngeal endoscopy. Then, all patients underwent a direct microlaryngoscopy with tumor biopsy and assessment of p53 gene mutations. Statistical analysis was performed correlating the presence of LPR, smoking status and mutations of p53, by chi-squared test and logistic regression analysis. Results: In 40% of the cases TP53 mutations were encountered. Sixteen transition mutations, 10 transversions, and 9 insertion-deletions were found. Furthermore, 22 missense, 4 frame deletions, 7 frame-shifts and 3 non-sense mutations were identified. In 34% of the patients pathologic LPR was recorded at 24h dual-probe-pH-monitoring and laryngeal endoscopy. A positive correlation between smoke and p53 mutations (p=.024, ?2 test) was found, while no correlations was recorded for LPR and p53 mutations (p>.05, ?2 test). LPR patients were at highest risk for tumors at the posterior glottic region (p=0.037, Fisher test). Conclusion: Our study highlighted a potential key role of LPR in the pathogenesis of laryngeal SSC in non smokers and non drinkers, especially for glottic cancer of the posterior region. Moreover, our findings seems to suggest the presence of different genetic mechanisms of biomolecular damage beside those due to smoking exposure, according to the low rate of the p53 tumor suppressor gene mutations in laryngeal SCC from patients with LPR.