Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer

Abstract

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.

High prevalence of and factors associated with human papillomavirus infection among women attending a tertiary hospital in Gauteng Province, South Africa

“…Although 70% of sexually active individuals are infected with HPV, the infection usually clears up within a few months, with 90% of cases clearing within two years after HPV acquisition [5]. However, 10 to 20% of HPV infections persist latently, leading to disease progression and eventually invasive cancer [6]. HPV messenger ribonucleic acid (mRNA) tests determine whether the virus is actively expressing the proteins responsible for oncogenesis in HPV infection [7] and thus allow the identification of transient and potentially transforming HPV infections [8].…”

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia

“…The main risk factor of cervical cancer is persistent HPV infection. It promotes impaired growth and differentiation of cells, leading to dysplasia (cervical intraepithelial neoplasia, CIN) [4]. We distinguished three grades of cervical dysplasia: CIN1 (LSIL; low-grade squamous intraepithelial lesion), CIN2, and CIN3 (classified together as HSIL; high-grade squamous intraepithelial lesion).…”

The exon 12‐containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway

“…Persistent infection with high‐risk human papillomavirus (HPV) genotypes is considered as the major cause of cervical cancer 4–6 . HPV infection may induce genomic alterations, such as copy number variation, DNA methylation, and somatic DNA mutation, which eventually contribute to cervical carcinogenesis 7,8 .…”

“…Persistent infection with high‐risk human papillomavirus (HPV) genotypes is considered as the major cause of cervical cancer. 4 , 5 , 6 HPV infection may induce genomic alterations, such as copy number variation, DNA methylation, and somatic DNA mutation, which eventually contribute to cervical carcinogenesis. 7 , 8 In addition to the abnormalities at transcriptome and epigenetic levels, recent studies have indicated that dysregulation of posttranscriptional splicing variants (alternative splicing) may also be associated with cervical cancer development and progression.…”