Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

Abstract

Introduction: Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. Areas covered: We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. Expert opinion: Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.

Novel high-resolution targeted sequencing of the cervicovaginal microbiome

“…Therefore, identifying individual species within the CVM may elucidate the roles of particular bacteria in the microbiome and provide alternative treatment strategies to prevent disease [ 74 ]. Furthermore, understanding the CVM change at this taxonomic rank may lead to identifying microbiome profiles that could act as predictive biomarkers for women at risk of developing cervical cancer [ 15 , 16 , 18 , 63 , 75 ]. Additional studies with a larger cohort of samples are needed to clarify whether the species or CST described in the current study possess such function and explain how they would associate with the effect of hrHPV infections.…”

“…Variations in the CVM have been widely described in relation to hrHPV infections, with CST IV significantly associated with high-grade cervical lesions and cancer [ 4 , 14 , 15 ]. Furthermore, recent investigations have determined that these microbiome alterations not only occur at the genus level but also at the species level, suggesting that specific microbial species and CST are associated with progressive or regressive behavior of cervical lesions and could act as biomarkers for the disease [ 16 – 18 ]. Nevertheless, studying the CVM and elucidating its function currently relies mostly on short length 16S rRNA gene sequencing (16S rRNA-seq), which struggles to distinguish microbes at this taxonomic rank [ 19 – 22 ].…”

Sensor detection in gynaecological medicine

“…As less than 8% of HPV infections lead to precancer, an ideal cervical cancer biomarker would indicate precancer progression before development into invasive carcinoma [29]. Current biomarker detection involves HPV DNA testing to identify HPV infection and therefore the possible presence of precancer or cancer [29,36]. This review presents select proteins, nucleic acids, and methylated DNA biomarkers related to cervical cancer and HPV infections (Table 2).…”

“…Although TOP2A expression was upregulated, it was not Please do not adjust margins Please do not adjust margins stage-dependent; p16's stage-dependent expression suggests it could be used as a prognostic biomarker [111]. While HPV testing has become a significant screening technique, it does not effectively predict prognosis since over 90% of HPV infections are cleared by the immune system [36]. In this case, ideal biomarkers would predict the likelihood of an HPV infection to transform into invasive carcinoma [36].…”

“…While HPV testing has become a significant screening technique, it does not effectively predict prognosis since over 90% of HPV infections are cleared by the immune system [36]. In this case, ideal biomarkers would predict the likelihood of an HPV infection to transform into invasive carcinoma [36]. As an HPV infection involves viral DNA integration into the host genome, the production of HPV oncoproteins affects the expression of some host proteins [29,36].…”