High Prevalence of Non-Vaccinated Oncogenic Human Papillomavirus Genotypes in High-Grade Squamous Intraepithelial Lesions of the Cervix: Thought-Provoking Results of a Detailed HPV Genotype Analysis

Abstract

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16-100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development.

Keywords: FFPE cone sample; HPV Direct Flow CHIP; HPV genotype profile; HSIL; PAP smear; nonavalent HPV vaccine.

Figure 1

PAP smear and FFPE cone samples originated from the same patient in all 49 cases. Variables are based on the agreement of the human papillomavirus genotype prevalence in the two sample types. Most of the samples (49.00%) belong to the compatible category with multi-HPV infections in PAP smears coupled with mono-HPV infection in FFPE cone samples. Identical: the detected HPV genotypes are exactly the same in the PAP smears and their FFPE cone sample pairs. Compatible: at least one of the genotypes detected in multi-PAP smears was also found in their FFPE cone sample pairs.