Over the years, the pace of developing vaccines for HBV and HPV has never stopped. After more than 30 years of application, the HBV vaccine has reduced 80% of hepatocellular carcinoma (HCC). However, vaccine escape variants occur under selective pressure induced by widespread vaccination and antiviral therapy, which results in fulminant infection and horizontal transmission. Several mechanisms have been studied to explain HBV vaccine escape, including vaccine escape mutations (VEMs) in the major hydrophilic region, which leads to a decrease in the binding ability to neutralize antibodies and is the primary escape mechanism, protein conformational and N‐linked glycosylation sites changes caused by VEMs, differences in genotype distribution, gene recombination, and some temporarily unknown reasons. However, effective solutions are still being explored. The HPV vaccine has also been proven to prevent 70%–90% of cervical cancer worldwide. Cases of HPV infection after being vaccinated have been observed in clinical practice. However, few researchers have paid attention to the mechanism of HPV vaccine escape. Thus, we reviewed the literature on vaccine escape of both HBV and HPV to discuss the mechanism of the virus escaping from vaccine protection and possible solutions to this problem. We analyzed the gap between studies of HPV and HBV and made prospects for further research in HPV vaccine escape.
Purpose: To evaluate the colposcopic accuracy of the detection of vaginal intraepithelial neoplasia (VaIN) according to the colposcopic terminology for the vagina from the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC). Methods: A total of 467 women who were suspected of having VaIN and underwent colposcopy at Obstetrics and Gynecology Hospital of Fudan University from January to December 2018 were included in this retrospective cohort study. The 2011 IFCPC revised terminology for the vagina was applied, and the agreement between colposcopic diagnosis and vaginal biopsy pathology was analysed. Results: Agreement between colposcopy and pathology was 69.16% (kappa=0.437, p< 0.001), with 23.34% overestimated and 7.49% underestimated diagnosis for colposcopy. The agreement was the lowest (35.71%) in the high-grade VaIN group, which was significantly different from that of other lesion grade groups (p< 0.01). Among grade 1 findings, thin acetowhite epithelium was the most frequent (80.51%). Grade 2 findings and vascular patterns were rare. The positive predictive values of the micropapillary pattern were 55.98% for low-grade VaIN and 5.98% for high-grade VaIN. The specificity of iodine negativity was 10.92% for low-grade VaIN and 8.30% for high-grade VaIN. There were significant differences in the maximum size of single lesions and in the number of lesions among different grade lesion groups. Conclusion: The agreement between colposcopy findings utilizing the 2011 IFCPC terminology and vaginal pathology is moderate, and more definite findings for high-grade VaIN may be needed. The micropapillary pattern can be considered an alternative low-grade finding, while iodine staining is nonspecific for all lesions. Scattered and spotty lesions suggest low-grade VaIN, while large single lesions suggest high-grade VaIN.
22 October 2024 in Frontiers in Cellular and Infection Microbiology
Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer.
As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.
1 February 2017 in Journal of Photochemistry and Photobiology A: Chemistry