Evaluation of clinical significance for multiple types of human papillomavirus (HPV) infection using various genomic analyses

Abstract

The purpose of this study was to evaluate the prevalence and distribution of human papillomavirus (HPV) in multiple abnormal lesions and assess the clinical significance of multiple types of HPV infection.

In total, 2,700 cases of cervicovaginal smear were reviewed and 258 cases (9.6%) with multiple-type HPV infection were selected. Among these 258 cases, 8 different tumor grades, 4 different tumor types, 1 discontinuous multiple abnormal legion, as well as 6 cervical intraepithelial neoplasia (CIN) I, 7 CIN II, and 7 CIN III single abnormal lesions, were selected. HPV DNA 9G chip genotyping, a REverse Blot hybridization assay, hybridcapture 2, an E6/E7 target mRNA RT-PCR assay, and clonal sequencing were all applied to validate HPV detection methods and compare the distribution of HPV types in cytology and tissue.

Women who were ≤29 years old or ≥70 years old showed higher rates of HPV infections. In addition, more multiple lesion cases with multiple HPV infection were noted (17 cases vs. 8 cases of multiple lesions in single HPV infections). In cases of multiple abnormal lesions, positive rates of HPV E6/E7 mRNA, which were detected in a RT-PCR assay, were 75.0% (6/8 cases) in low grade cervical lesions, whereas HPV E6/E7 mRNA positivity was 33.3% (2/6) in low grade cervical lesions of a single abnormal lesion.

Multiple-type HPV infection and age could be a risk factor for the development of uterine cervical cancer. We recommend that young women with multiple types of HPV infection should be followed up more closely. Here, a RT-PCR assay was used to detect that positive rates of HPV E6/E7 mRNA were higher in low grade cervical lesions with multiple abnormal lesions compared with those in a single abnormal lesion. Therefore, we also suggest that results of HPV E6/E7 mRNA RT-PCR assays could be used as a triage for screening strategies or patient management.