Background
The Papillomaviridae family includes the non-enveloped double-stranded DNA virus known as the human papillomavirus (HPV). HPV infection primarily occurs in the keratinocytes of the skin and mucous membranes, with most infections not causing serious disease. However, among the nearly 200 different HPV strains, certain high-risk types, particularly HPV 16, 18, and 31, are closely associated with malignant tumors, including cervical cancer, anal cancer, and oropharyngeal cancer. HPV 31 is a high-risk type and is considered one of the carcinogenic HPV strains. Its infection can lead to cervical cancer and other precancerous lesions. The oncogenic mechanism of HPV primarily involves its early genes (such as E6 and E7), which interfere with the normal cell cycle by inhibiting tumor suppressor genes like p53 and Rb, thereby inducing cellular transformation. During HPV's lifecycle, its genome maintains a low-copy number state within host cells, gradually amplifying viral DNA, leading to alterations in the host cell's division process. The L1 capsid protein of HPV 31 is a critical component of the virus particle. L1 is the major structural protein of the HPV capsid and can spontaneously form icosahedral virus-like particles (VLPs), which are the foundation of modern HPV vaccines. The L1 protein is highly conserved across different subtypes, offering a stable antigenic basis for vaccine development. However, variations in the surface loops of L1 may contribute to HPV's ability to evade host immune responses. HPV 31 L1 protein has strong immunogenicity, capable of inducing humoral immunity and generating neutralizing antibodies. Studies have shown that VLPs formed by the self-assembly of L1 proteins can effectively mimic the antigenic epitopes of natural viruses, making them widely used in the development of HPV vaccines. L1 proteins assemble into 72 capsomeres, with each pentamer consisting of five L1 monomers. Although the L2 protein plays a lesser role in vaccines, it is also involved in aiding viral infection.
The structural characteristics of HPV 31 L1 protein underscore its crucial role in HPV vaccines. Vaccines based on the L1 protein, such as Merck's Gardasil series, are widely used to prevent HPV-related cancers and diseases. These vaccines work by inducing the production of neutralizing antibodies against HPV L1 protein, thereby neutralizing the virus before it enters host cells and preventing infection. The L1 protein's high conservation across subtypes suggests potential for broad-spectrum vaccine development. However, variability in surface loops indicates HPV's capacity to evade neutralizing antibody responses elicited by prior infections. Overcoming this immune evasion issue is a major challenge in developing vaccines that target multiple HPV subtypes. In addition to its structural proteins, HPV 31's pathogenic mechanism also includes the roles of its early genes in host cells. E6 and E7 proteins are the primary factors responsible for HPV 31-induced carcinogenesis in host cells. E6 binds to the tumor suppressor protein p53, promoting its degradation and thereby inhibiting apoptosis. E7 binds to the retinoblastoma protein (pRb), releasing E2F transcription factors, which drive uncontrolled cell cycle progression. These molecular mechanisms play critical roles in the development of HPV-related cancers.
Several vaccines targeting high-risk HPV strains, including HPV 31, are currently available. These vaccines, which induce the production of potent neutralizing antibodies via L1 protein, effectively block viral entry into host cells. Preventive vaccines significantly reduce the incidence of HPV-related diseases, particularly cervical cancer. These vaccinations do not, however, cure pre-existing HPV infections. Therefore, early screening and diagnosis are crucial for controlling the development of HPV-related cancers. In addition to vaccination, molecular detection of HPV is an important strategy for managing HPV-related diseases. HPV infection is typically detected using molecular biology techniques such as PCR and nucleic acid hybridization. These methods provide accurate genotyping and quantification of HPV infections, offering critical clinical insights. HPV DNA testing is currently the most widely used detection method, accurately identifying the type and viral load of HPV infections, and monitoring the duration of infection—important for assessing disease progression and prognosis. Overall, HPV 31 L1 protein plays an essential role in HPV vaccine development. The virus-like particle (VLP) technology based on the L1 protein has been successfully applied to the development and clinical application of several HPV vaccines, providing an effective global solution for preventing HPV-related diseases. As research progresses, our understanding of HPV 31's pathogenic mechanisms, immune evasion, and vaccine prevention will deepen, bringing new hope for preventing and treating HPV-related cancers.
Figure 1. Flowchart for testing, selecting, and processing naturally infected female donors to produce seven candidate international standards for HPV antibodies (Source: Kemp TJ, et al., 2024)
Alternative Names
Anti-human papillomavirus 31 L1 antibody
HPV31 L1 monoclonal antibody
Anti-HPV L1 protein antibody
References
- 1. Kemp TJ, et al. WHO International Standards for antibodies to HPV6, HPV11, HPV31, HPV33, HPV45, HPV52, and HPV58. npj Vaccines. 2024;9:165.