Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.
Summary. Background: Survival of oropharyngeal squamous cell carcinoma (OSCC) patients depends on the risk and environmental factors, tumor biology, achievements in diagnostics and treatment approaches. Aim: To perform a survival analysis of the patients with OSCC treated over a 10-year period in a single hospital in Latvia linking these data to histopathological findings, risk factors and received therapy. Materials and Methods: The main outcome measures were overall and disease-specific survival (OS and DS) along with histopathology analysis. Results: Kaplan – Meier survival analysis showed better survival for females, younger patients lacking bad habits, operated and received radiotherapy, with lower T grade and disease stage. Cox regression showed diminished early death risk in patients with lower T grade, no regional metastases (N0) and bad habits, operated and received radiotherapy. A vast majority of tumors were localized in palatine tonsils and the base of the tongue. The localization did not correlate with mean survival time/survival. Lower OS (p = 0.03) and DS (p = 0.026) were estimated for patients with pharyngeal wall and tonsillar involvement compared to tumors localized in the soft palate. A histological variant of tumor seemed irrelevant estimating OS and DS, whereas therapeutic modalities significantly affected survival. Conclusions: OSCC patients with lower T grade, N0 status, lacking bad habits, and surgically treated had better survival.
The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.
Oropharynx is one of the most common localizations for malignant neoplasms in the head and neck region. HPV-positive OPSCCs are the most common subtypes in Western countries with tobacco and alcohol use, remaining the major risk factors for cancer development in this region. The study aims to address the significance of smoking and alcohol abuse in OPSCC cases and perform a survival analysis of the patients with OPSCC treated over a 10-year period in a single hospital in Latvia, correlating these data with patients' hazardous habits (smoking and alcohol abuse). Out of 247 patients, the majority were smokers (75.95%, n = 180), approximately one third were habitual drinkers (35.19%, n = 82) or were exposed to both aforementioned major risk factors (31.47%, n = 73). Kaplan-Meier survival analysis showed significantly better survival for the patients without the aforementioned hazardous habits. Cox regression analysis proved a higher early death rate when both factors (smoking and alcohol abuse) were present. It seems that smoking has a higher predictive value than alcohol abuse.
The incidence of hypopharyngeal cancer globally is about 0.8 per 100 000. Globally, approximately 38 000 cases of head and neck cancer are considered yearly to be high-risk human papillomavirus (HR-HPV) related. Biopsy material fixation in formalin and embedding in paraffin (FFPE) creates many challenges. The extraction of nucleic acid material requires a more complicated approach, and often the extracted DNA is fragmented. The aim of the study was to compare several HR-HPV detection methods in nucleic acid material extracted from FFPE samples. The extracted DNA was analysed with different molecular biology methods to assess DNA quality and to determine the presence of HPV DNA with various HPV detection systems. The results were compared and statistically analysed. There was good agreement between two real-time PCR methods — Anyplex II HPV28 and Sacace HPV High-Risk Screen Real-TM Quant. We failed to reach a conclusion on agreement between real-time PCR methods and HPV16 type-specific primer PCR. There was moderate positive correlation between Anyplex II HPV28 semiquantitative results and Sacace quantitative results. We suggest that real-time PCR assays detecting smaller DNA amplicons are good and reliable methods for detecting HPV genetic material in FFPE samples.
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