Objective: To investigate the clinical and prognostic significance of human papillomavirus (HPV) in a Chinese population of cervical cancers. Methods: We studied 121 cervical cancer tissue samples from patients treated at our hospital. Identification and typing of HPV were done by polymerase chain reaction (PCR) using consensus primers MY11 and MY09 followed by direct DNA sequencing. The results were correlated with various clinical and prognostic parameters. Results: We found HPV DNA in 95 (78.5%) cases, including HPV-16 in 59 (48.8%) and HPV-18 in 14 (11.6%) cases. χ2 analysis revealed no significant correlation between the presence of HPV DNA and age at diagnosis, clinical stage, histologic type, tumor grading, 2-year and 5-year survival rate. Of the factors evaluated, age at diagnosis and histologic type were found to have a statistically significant relationship with HPV type. The mean age of the HPV-18 group was 48.6 years compared to 57.1 years for the HPV-16 group (p = 0.045) and 58.2 years for the HPV-negative group (p = 0.04). HPV-18 was detected more often in adenocarcinomas (AC) than in squamous cell carcinomas (SCC). Conversely HPV-16 was detected significantly more often in SCC (p < 0.0001). The HPV-negative group also had a higher incidence of SCC (p = 0.007). HPV-18-positive patients seemed to have more nodal involvement than both HPV-16-positive patients (45.5 vs. 20.8%) and HPV-negative patients (45.5 vs. 18.2%); however, it did not reach statistical significance. Conclusions: These observations suggest that the presence of HPV DNA does not bear any clinical or prognostic significance in a Chinese population of cervical cancers. HPV-18 is found more often in younger patients and is associated with AC.
Infection with specific genotypes of human papillomavirus (HPV) has been strongly implicated in cervical carcinogenesis. However, HPV infection alone is insufficient for malignant transformation of the cervical epithelium. An alteration of microsatellite repeats is the result of slippage owing to strand misalignment during DNA replication and is referred to as microsatellite instability (MSI). These defects in DNA repair pathways have been related to human carcinogenesis; however, the role of MSI in the tumorigenesis of cervical cancer remains unclear. The clinical and pathological features of cervical cancers which are MSI-positive have also not been fully characterized. This study investigated the prevalence of MSI in cervical cancer and its relationship to clinico-pathological characteristics and HPV infection. Polymerase chain reaction-based microsatellite assay combined with tissue microdissection was used to examine for MSI in 50 cervical squamous cell carcinomas in Hong Kong women. In addition, the immunohistochemical staining was performed to determine the expression of major DNA mismatch repair genes, hMSH2 and hMLH1. Six cases (12%) displayed a low frequency of MSI (MSL-L) showing MSI at one locus only in 5 loci examined. Seven cases (14%) showed a high frequency of MSI (MSI-H) having MSI at 2 or more loci. Grouping MSI-L and MSI-H cases together as MSI-positive, statistical analysis of HPV infection, tumor grade, clinical stage and clinical status failed to disclose differences between MSI-positive and MSI-negative cases (p > 0.05). However, MSI-H correlated with advanced stage of disease (p < 0.05). Individuals with MSI-H tumors appeared to have reduced overall survival compared to individuals with MSI-L and MSI-negative tumors, but the difference was not statistically significant (p = 0.059). An absence of either MSH2 or MLH1 expression was observed in 2 MSI-L and 4 MSI-H cases, respectively. The results suggest that MSI is present in a subgroup of cervical squamous cell carcinomas, and defects resulting in MSI may be related to tumor progression and possibly poor prognosis in cervical cancer.
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