HPV Genotyping by Molecular Mapping of Tissue Samples in Vaginal Squamous Intraepithelial Neoplasia (VaIN) and Vaginal Squamous Cell Carcinoma (VaSCC).

Shitai Zhang,Kaori Okayama,Mayumi Saito,Nozomu Kurose,Jinichi Sakamoto,Mitsuaki Okodo,Toshiyuki Sasagawa

doi:10.3390/cancers13133260

Abstract

Simple SummaryHPV genotypes were determined in 63 vaginal intraepithelial neoplasia (VaIN) and 7 vaginal squamous cell carcinomas (VaSCC). Of these, 37 cases had VaIN alone, and 26 cases had both VaIN and cervical intraepithelial neoplasia (CIN) or condyloma. HPV typing was performed in scraped cells by Genosearch-31 and in the archived tissues by uniplex E6/E7 PCR. In a total of 49 VaIN1, 17 VaIN2/3, and 7 VaSCC tissues, the prevalence of HPV was 91.2% in VaIN and 85.7% in VaSCC. Comparing HPV results in scraped cell and tissue, 46.2% of high-risk (HR) types and 68.1% of any HPV types that had been identified in cell samples were not present in corresponding tissues. HPV types in VaIN and CIN lesions differed in 92.3% of cases with multiple lesions. These results suggest that there are many preclinical HPV infections in the vagina or the cervix, and VaIN and CIN are independently developed. The manual microdissection procedure of tissue revealed one HPV type in one lesion. The vagina appears to be the reservoir for any mucosal HPV type, and HR- or pHR-HPV types are causative agents for vaginal malignancies.HPV genotypes were determined in 63 vaginal intraepithelial neoplasia (VaIN) and 7 vaginal squamous cell carcinomas (VaSCC). Of these, 37 cases had VaIN alone, and 26 cases had both VaIN and cervical intraepithelial neoplasia (CIN) or condyloma. HPV typing was performed in scraped cells by Genosearch-31 (GS-31) and in the archived tissues by uniplex E6/E7 PCR. In a total of 49 VaIN1, 17 VaIN2/3, and 7 VaSCC tissues, the prevalence of HPV was 91.2% in VaIN (VaIN1: 87.8%, VaIN2/3: 100%) and 85.7% in VaSCC. Comparing HPV results in scraped cell and tissue, 46.2% of high-risk (HR) types and 68.1% of any HPV types that had been identified in cell samples were not present in corresponding tissues. HPV types in VaIN and CIN lesions differed in 92.3% (24/26) of cases with multiple lesions. These results suggest that there are many preclinical HPV infections in the vagina or the cervix, and VaIN and CIN are independently developed. The manual microdissection procedure of tissue revealed one HPV type in one lesion. Seventeen HPV types, including high-risk (HR), possible high-risk (pHR), and low-risk (LR), were identified in 43 VaIN1 lesions. In higher grade lesions, six HR (HPV16, 18, 51, 52, 56, 58), one pHR (HPV66), and one LR (HPV42) HPV types were identified in 17 VaIN2/3, and six HPV types, including HPV16, 45, 58, and 68 (HR), and HPV53 and 67 (pHR), were detected in each case of VaSCC. The vagina appears to be the reservoir for any mucosal HPV type, and HR- or pHR-HPV types are causative agents for vaginal malignancies.

Highlights

Human papillomavirus (HPV) has been proven to be the causative agent of cervical cancer and its precancerous lesions, this virus belongs to the Papillomaviridae family, which is a small, non-enveloped type, double-strand DNA virus group [1]
It was shown that 88.2% (15/17) of VaIN2/3 and 28.6% (14/49) of VaIN1 were positive for p16 expression, whereas this was seen in only 9.5% of normal glandular or metaplastic cells, and no expression was found in normal squamous epithelium adjacent to vaginal intraepithelial neoplasia (VaIN) or cervical intraepithelial neoplasia (CIN)
Most VaIN1 cases (92.6%, 13/14) positive for p16 expression were infected with HR or possible high-risk (pHR)-HPV types, only one p16-positive VaIN1 was infected with an LR-HPV type, namely, HPV71

Summary

Introduction

Human papillomavirus (HPV) has been proven to be the causative agent of cervical cancer and its precancerous lesions, this virus belongs to the Papillomaviridae family, which is a small, non-enveloped type, double-strand DNA (dsDNA) virus group [1]. On the basis of their association with premalignant and malignant lesions, 13 HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) have been defined as high-risk (HR), HPV68 is categorized as a probable high-risk type [8]. An additional nine HPV types (HPV26, 30, 34, 53, 66, 67, 70, 73, and 82), which belong to alpha-5, 6, 7, 9 and 11 genera, are thought to be possible high-risk HPV (pHR) types because these types are identified in cancer tissue [9]. It is thought that such actions are generally not present in low-risk (LR) HPV types

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