Accuracy of liquid-based brush cytology and HPV detection for the diagnosis and management of patients with oropharyngeal and oral cancer.

OBJECTIVES: This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment. MATERIAL AND METHODS: Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed. RESULTS: Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment. CONCLUSIONS: Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment. CLINICAL RELEVANCE: Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines.

Oral premalignant lesions of smokers and non-smokers show similar carcinogenic pathways and outcomes. A clinicopathological and molecular comparative analysis.

BACKGROUND: Oral premalignant lesions (OPML) are frequently extensive and multifocal leading high morbidity for patients. Although oral squamous carcinoma (OSCC) in non-smoker patients is increasing, little is known about OPML and the carcinogenesis process in these patients. The aims of the study were to insight and compare the clinicopathological and molecular characteristics of OPML of non-smoker and smoker patients from which one or multiple OSCC have developed. METHODS: Eighty-one patients showing extensive and/or multifocal OPML were included in the survey. HPV and EBV were investigated by PCR and in situ hybridization respectively. Cytogenetic studies were performed by microarray in sequential progressive 30 lesions; p53 expression was investigated by immunohistochemistry. RESULTS: The patients were 41 males and 40 females, ages ranging from 32 to 93 years (median 64); 43 (53%) were smokers. Non-smokers were more frequently female with a median age of 68, whereas smokers were men with a median age of 60 (P = 0.005). HPV and EBV were negative in all cases. The most consistent and earliest cytogenetic alterations in both non-smokers and smokers were loss of heterozygosity (LOH) and losses of locus harboring tumor suppressor genes. Progression to high-grade dysplasia and OSCC showed progressive addition of LOH, tumor suppressor losses, and oncogenic gains. CONCLUSION: Non-smoker patients are mostly elderly female and show oral carcinogenic pathways and outcomes similar to smoker patients.

Enrichment of Cells with Cancer Stem Cell-Like Markers in Relapses of Chemoresistant Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. METHODS: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR). Differences in expression between the first and second specimens were assessed. RESULTS: Expression between the first and second specimens varied as follows: CD44 increased by 14.67% (95% confidence interval, CI: 6.94 to 22.40; p < 0.01); HLA-I decreased by 16.72% (95% CI: -23.87 to -9.47; p < 0.01); pancytokeratin decreased by 24.91% (95% CI: -32.8 to -17.7; p < 0.01), and p-EFGR expression decreased by 12.30% (95% CI: -20.61 to -3.98; p < 0.005). CONCLUSIONS: Among patients with HNSCC, there is an enrichment of cells with stem-like markers in relapsed tumors when compared with the primary tumor. This finding should be considered when developing treatment strategies.

p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas.

High-grade neuroendocrine carcinomas (HGNECs) of the head and neck have the morphological appearance of undifferentiated carcinomas and could be histologically similar to human papillomavirus (HPV)-associated non-keratinizing squamous cell carcinomas of the head and neck. The aim of the study is to characterize histologically, immunohistochemically, and virologically these unusual neoplasms. Nineteen HGNECs of the head and neck (1 oropharyngeal, 5 sinonasal, 7 of the larynx, and 6 of the parotid gland) were reviewed and analyzed with a immunohistochemical panel, with special emphasis on cell cycle proteins. The tumors were tested for HPV by in situ hybridization (GenPoint HPV, Dako) and PCR (SPF10-DEIA-LiPA25). Merkel cell polyomavirus was studied using the antibody CM2B4. Fifteen HGNEC were of small cell and 4 of large cell type. Most of the tumors (14/19, 73.7 %), including all the pure small cell carcinomas, showed a strong and diffuse positive staining for p16. Eleven of them (78.5 %) had Rb loss and a low or absent cyclin D1 expression. All cases were negative for HPV and polyomavirus. Most patients were smokers, diagnosed at advanced stages of the disease, and had a poor outcome, with a 5-year survival of 18 %. In conclusion, HGNECs of the head and neck are infrequently related to HPV infection, but usually show strong, diffuse positive p16 immunostaining due to Rb pathway dysregulation. Awareness of this immunohistochemical pattern of expression may avoid a potential diagnostic pitfall with HPV-associated non-keratinizing squamous cell carcinomas, which have a better prognosis.