High-risk human papillomavirus
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High-Risk Human Papillomavirus: Oncogenesis, Screening, and Prognosis
High-Risk HPV and Oncogenesis
High-risk human papillomavirus (hrHPV) is a significant etiological agent in various cancers, most notably cervical cancer. The viral oncogenes E6 and E7 play a crucial role in the oncogenic process by targeting key cellular pathways. E6 and E7 disrupt the functions of tumor suppressor proteins p53 and pRb, respectively, leading to uncontrolled cell proliferation and carcinogenesis. Additionally, these oncogenes can alter epigenetic marks and splicing changes, further contributing to cancer development .
Screening for High-Risk HPV
The effectiveness of hrHPV testing as a primary screening method for cervical cancer has been demonstrated in various studies. A large-scale clinical trial in China showed that hrHPV testing is more effective than traditional cytology and visual inspection methods in detecting high-grade cervical intraepithelial neoplasia (CIN2+ and CIN3+). The study found that hrHPV testing, followed by appropriate triage methods, significantly improved disease detection rates and reduced unnecessary colposcopy referrals.
Prognostic Value in Anal and Head and Neck Cancers
High-risk HPV is also implicated in anal squamous cell carcinomas (ASCC) and head and neck squamous cell carcinomas (HNSCC). In ASCC, the presence of hrHPV DNA and p16INK4a expression is associated with better overall survival rates. Similarly, HPV-positive HNSCCs, particularly those in the oropharynx, have distinct clinical and pathological features and are associated with a better prognosis compared to HPV-negative tumors.
HPV in Immunocompromised Individuals
Immunocompromised individuals, including those with primary immunodeficiencies or HIV infection, are at higher risk for persistent hrHPV infections and subsequent cancer development. These individuals often experience treatment-refractory and progressive HPV-related diseases. The immune evasion strategies employed by hrHPV, such as interfering with antigen presentation and cytokine production, contribute to the persistence of the virus in these hosts .
Emerging Therapies and Future Directions
Current treatments for HPV-related cancers include surgery, chemotherapy, and radiotherapy. However, new therapeutic approaches are being explored, including RNA-based therapies targeting the HPV genome or mRNA transcripts. Additionally, therapeutic vaccines and immune checkpoint inhibitors like anti-PD-1 therapy are under investigation to improve outcomes in HPV-associated malignancies.
Conclusion
High-risk HPV plays a critical role in the development of several cancers through its oncogenes E6 and E7, which disrupt key cellular pathways. Effective screening methods, such as hrHPV testing, have improved early detection and management of cervical cancer. The prognostic value of hrHPV in anal and head and neck cancers highlights the importance of HPV status in clinical outcomes. Immunocompromised individuals remain a high-risk group for persistent HPV infections and associated cancers, necessitating the development of advanced therapeutic strategies. Continued research into the molecular mechanisms of HPV and the development of next-generation therapies holds promise for better management and treatment of HPV-related diseases.
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