Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer

Abstract

Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.

Keywords: biomarkers; cervical cancer; human papillomavirus; prevention; screening.

Figure 1

HPV life cycle and CC progression. The HPV life cycle begins with infection of basal epithelial cells, where the virus undergoes low-level replication. As the cells differentiate, the viral oncogenes are gradually expressed, leading to uncontrolled host cell proliferation. The virus then assembles and is released from differentiated epithelial cells. Persistent infection with HR-HPV types can cause CIN, progressing from mild (CIN1) to severe abnormalities (CIN3). Without timely reversal or treatment, this can ultimately develop into invasive CC. The image was created with BioRender.

Figure 2

HPV genome and its function in CC pathogenesis. (A) Structure and arrangement of the HPV16 genome. (B) The E6 protein recruits E6AP to promote the ubiquitination of p53, leading to its degradation, thereby inhibiting apoptosis; the E7 protein binds to pRb, releasing E2F from the pRb–E2F complex, thereby causing uncontrolled cell proliferation. Ub, ubiquitin. The image was created with BioRender.

Figure 3

Cancer screening for HPV-infected patients. HPV⁻ individuals can undergo regular screening, while HPV⁺ patients are categorized based on the types of HPV infection. The HPV16/18⁺ patients undergo colposcopy directly, while those positive for other 12 types of HR-HPV require further evaluation based on cytology results.

Figure 4

Treatment opportunities for CC patients with HPV infection. Immunotherapy, therapies targeting E6 and E7 oncogenes and mRNA, and HPV vaccines represent promising new treatment approaches for CC. The image was created with BioRender.