Abstract
Backgroundp16INK4A expression has been used as a surrogate marker for human papillomavirus (HPV) infection in cervical cancer and head and neck cancer. p53 has also been reported as a feasible marker to identify HPV-positive oropharyngeal carcinoma and penile lesions. This study aimed to investigate p16INK4A and p53 expression levels and their correlation with HPV status and clinical parameters in Kazakh patients with esophageal squamous cell carcinoma.MethodsImmunohistochemical expression of p16INK4A and p53 were evaluated in 163 cases of esophageal squamous cell carcinoma in Kazakh patients. The presence of HPV DNA was detected by polymerase chain reaction.Resultsp16INK4A-positive expression was detected in 19.0 % of patients, and its expression was significantly correlated with a lower frequency of lymph node metastasis (p = 0.038). By contrast no significant association was found between p16INK4A-positive expression and HPV status (correlation coefficient = -0.062, p = 0.499). p16INK4A-positive expression did not affect the odds of tumors being HPV positive (odds ratio [OR] = 0.727 with 95 % confidence interval [CI] = 0.288–1.836). The sensitivity of p16INK4A-positive expression as an HPV marker was 0.164, with a specificity of 0.788 and a positive predictive value of 0.391. p53-positive expression was present in 88.3 % of all cases. Although no significant correlation with available clinical parameters was found, a significantly inverse correlation was observed between p53 expression and HPV status (correlation coefficient = -0.186, p = 0.039). Moreover, p53-positive expression decreased the odds of tumors being HPV positive (OR = 0.292 with 95 % CI = 0.086–0.990). The sensitivity of p53-negative expression as an HPV marker was 0.179, with a specificity of 0.940 and a positive predictive value of 0.714. The overall HPV prevalence was high (45.5 %) in Kazakh patients, with no significant association between HPV positivity and available clinical parameters or combined p16INK4A/p53 expression.Conclusionsp16INK4A-positive expression was associated with lymph node metastasis. Results indicate that p53-negative expression and not p16INK4A-positive expression may be used as a marker for HPV status in ESCC; however, this finding requires further studies for validation.
Highlights
Esophageal cancer (EC), is one of the most common malignancies and the sixth most frequent cause of cancer-related death worldwide with a global number of 400,000 deaths in 2012
This study aimed to investigate p16INK4A and p53 expression levels and their correlation with Human papillomavirus (HPV) status and clinical parameters in Kazakh patients to raise the possibility of using them as surrogate markers of HPV infection in ESCC
Immunohistochemical expression of p16INK4A in correlation with clinical parameters and HPV status in Kazakh patients with ESCC A total of 158 ESCC samples were analyzed for p16INK4A expression through immunohistochemistry, with 30 (19.0 %) and 128 (81.0 %) showing positive and negative expressions, respectively (Fig. 1)
Summary
Esophageal cancer (EC), is one of the most common malignancies and the sixth most frequent cause of cancer-related death worldwide with a global number of 400,000 deaths in 2012 (http://globocan.iarc.fr/ Default.aspx). Several studies have demonstrated that HPV infection is the main cause of cervical cancer and head and neck cancer [4, 5]. HPV infection in esophageal cancer was first reported in 1982 based on histological observations [6]. It has been reported that the HPV prevalence in ESCC of Kazakh patients ranged from 30 % to 66.67 % [10,11,12]. For such reason the identification of HPV status in the ESCC lesions is important to establish their etiology and prognostic significance [13]
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