The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications

Abstract

Cervical cancer is the third most common cancer in women worldwide, with concepts and knowledge about its prevention and treatment evolving rapidly. Human papillomavirus (HPV) has been identified as a major factor that leads to cervical cancer, although HPV infection alone cannot cause the disease. In fact, HPV-driven cancer is a small probability event because most infections are transient and could be cleared spontaneously by host immune system. With persistent HPV infection, decades are required for progression to cervical cancer. Therefore, this long time window provides golden opportunity for clinical intervention, and the fundament here is to elucidate the carcinogenic pattern and applicable targets during HPV-host interaction. In this review, we discuss the key factors that contribute to the persistence of HPV and cervical carcinogenesis, emerging new concepts and technologies for cancer interventions, and more urgently, how these concepts and technologies might lead to clinical precision medicine which could provide prediction, prevention, and early treatment for patients.

Keywords: Cervical carcinogenesis; HPV integration; NGS‐based HPV testing; cervical screening; genome editing tools.

Figure 1

Estimated age‐standardized rates (World) of incidence cases, females, cervical cancer, worldwide in 2012. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization/International Agency for Research on Cancer concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate borderlines for which there may not yet be full agreement.

Figure 2

Estimated age‐standardized rates (World) of deaths, females, cervical cancer, worldwide in 2012. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization/International Agency for Research on Cancer concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate borderlines for which there may not yet be full agreement.

Figure 3

HPV testing methods for cervical screening timeline. Brief overview of screening practice based on HPV changes and related discoveries. FDA, Food and Drug Administration; HPV, human papillomavirus.

Figure 4

Genome editing as a therapeutic strategy for HPV infections. Diagram of HPV genome editing using ZFNs, TALENs, and CRISPR/Cas9.