About this Research Topic
Papillomaviruses (PV) are non-enveloped, double-stranded circular DNA viruses infecting the epithelium of different vertebrate species. Based on genomic similarities, more than 300 PV types have been classified so far, with more than 200 genotypes infecting humans (HPV). According to the International Agency of Research on Cancer (IARC), a subset of high-risk HPV is classified as human carcinogens.
PV infection of mucosal or cutaneous epithelium causes mostly asymptomatic and spontaneously regressing infections. Viral infection is primarily established in basal keratinocytes through a series of maturation events and cell entry pathways that are still under elucidation. Once the infection is established, PV deregulate a variety of cellular pathways to influence cellular proliferation, apoptosis and genomic stability, leading to host cell hyperproliferation and transformation. Through the use of specific host cell factors, PV replication strictly depends on the epithelial differentiation program, which is also one of the mechanisms for passively evading immune vigilance. Limited interaction with the host immune system and low expression levels especially of the viral oncoproteins results in generally poor and slow immune responses against PV. Therefore, upon natural infections, protective humoral immunity is mostly induced by PV type-specific neutralising antibodies against the major capsid protein L1. However, clearance of PV-infected cells and lesions requires activation of effective T cell responses.
Mucosal infections with low-risk HPV can cause hyperproliferations like anogenital warts and recurrent respiratory papillomatosis. Conversely, high-risk PV induce intraepithelial neoplasias that may further progress to cancer. Persistent infections with high-risk HPV are accountable for about 5% of all human malignancies, causing more than half a million deaths annually. Here, the proportion of cancers attributable to HPV varies greatly: practically 100% of cervical cancers are attributable to HPV infections compared to 25-90 % for different anogenital and about 30% of oropharyngeal cancers.
HPV infection of the skin, which is known to be ubiquitously colonised by a plethora of cutaneous HPV types, rarely causes severe disease in the immunocompetent. This may change along the individual’s lifetime and in the immunosuppressed and after chronic sun exposure certain carcinogenic cutaneous HPV can favour the development of keratinocyte cancer via a hit-and-run mechanism that is still not fully understood. Many pathways, co-factors and conditions that support development of HPV-related cancers are known. Nevertheless, many knowledge gaps are yet to be filled to explain why some HPV-positive individuals develop HPV-associated cancers while others do not.
Despite the availability prevention measures against at least some HPV-related malignancies, their delivery is still an unresolved issue in many countries of the world. Prophylactic HPV vaccines were licensed more than a decade ago, have shown excellent safety and efficacy profiles and are indicated for young adolescents. They induce high levels of long-lasting HPV type-specific antibodies that protect against persistent infections, intraepithelial lesions and cancers. However, they have limited cross-protectivity, and further, no therapeutic vaccine for treatment of HPV-associated pathologies has been approved. Clinically approved HPV vaccines against cutaneous HPV types are also missing, but several developments for broadly cross-protective next generation vaccines are in advanced stages.
The goal of the current themed article collection is to promote publishing in papillomavirus research, to spotlight novelty and to drive advancements in the field. Contributions to other topics not specifically addressed above, but focused on the scope described below, are surely welcome as well.
This Research Topic welcomes original and insightful scientific contributions in the format of Original Article, Mini-Review, Brief Communications, Hypothesis and Theory, Perspective and Opinion covering the themes PV diversity, infection and replication, immunity against PV and HPV vaccines. Specific topics of interest in this issue include, but are not limited to:
- PV biology (genotypic diversity, mechanisms of infection, replication and latency)
- Mechanisms of innate and adaptive immunity against PV and how it can be evaded
- PV-related tumorigenesis (molecular mechanisms of PV-driven cellular proliferation and carcinogenesis, co-factors associated with the development of HPV-associated cancers)
- HPV-induced cancers (anogenital cancer, head-and-neck cancers, non-melanoma skin cancer)
- Prospects and challenges on the currently available HPV vaccination programs, and next generation HPV vaccines (sustainability and mechanisms of long-term immunity, modelling of HPV evolution in post-vaccination era, global challenges in delivery of HPV vaccines, effect of pandemic settings and lockdowns on prevention of HPV-associated cancers)
PV infection of mucosal or cutaneous epithelium causes mostly asymptomatic and spontaneously regressing infections. Viral infection is primarily established in basal keratinocytes through a series of maturation events and cell entry pathways that are still under elucidation. Once the infection is established, PV deregulate a variety of cellular pathways to influence cellular proliferation, apoptosis and genomic stability, leading to host cell hyperproliferation and transformation. Through the use of specific host cell factors, PV replication strictly depends on the epithelial differentiation program, which is also one of the mechanisms for passively evading immune vigilance. Limited interaction with the host immune system and low expression levels especially of the viral oncoproteins results in generally poor and slow immune responses against PV. Therefore, upon natural infections, protective humoral immunity is mostly induced by PV type-specific neutralising antibodies against the major capsid protein L1. However, clearance of PV-infected cells and lesions requires activation of effective T cell responses.
Mucosal infections with low-risk HPV can cause hyperproliferations like anogenital warts and recurrent respiratory papillomatosis. Conversely, high-risk PV induce intraepithelial neoplasias that may further progress to cancer. Persistent infections with high-risk HPV are accountable for about 5% of all human malignancies, causing more than half a million deaths annually. Here, the proportion of cancers attributable to HPV varies greatly: practically 100% of cervical cancers are attributable to HPV infections compared to 25-90 % for different anogenital and about 30% of oropharyngeal cancers.
HPV infection of the skin, which is known to be ubiquitously colonised by a plethora of cutaneous HPV types, rarely causes severe disease in the immunocompetent. This may change along the individual’s lifetime and in the immunosuppressed and after chronic sun exposure certain carcinogenic cutaneous HPV can favour the development of keratinocyte cancer via a hit-and-run mechanism that is still not fully understood. Many pathways, co-factors and conditions that support development of HPV-related cancers are known. Nevertheless, many knowledge gaps are yet to be filled to explain why some HPV-positive individuals develop HPV-associated cancers while others do not.
Despite the availability prevention measures against at least some HPV-related malignancies, their delivery is still an unresolved issue in many countries of the world. Prophylactic HPV vaccines were licensed more than a decade ago, have shown excellent safety and efficacy profiles and are indicated for young adolescents. They induce high levels of long-lasting HPV type-specific antibodies that protect against persistent infections, intraepithelial lesions and cancers. However, they have limited cross-protectivity, and further, no therapeutic vaccine for treatment of HPV-associated pathologies has been approved. Clinically approved HPV vaccines against cutaneous HPV types are also missing, but several developments for broadly cross-protective next generation vaccines are in advanced stages.
The goal of the current themed article collection is to promote publishing in papillomavirus research, to spotlight novelty and to drive advancements in the field. Contributions to other topics not specifically addressed above, but focused on the scope described below, are surely welcome as well.
This Research Topic welcomes original and insightful scientific contributions in the format of Original Article, Mini-Review, Brief Communications, Hypothesis and Theory, Perspective and Opinion covering the themes PV diversity, infection and replication, immunity against PV and HPV vaccines. Specific topics of interest in this issue include, but are not limited to:
- PV biology (genotypic diversity, mechanisms of infection, replication and latency)
- Mechanisms of innate and adaptive immunity against PV and how it can be evaded
- PV-related tumorigenesis (molecular mechanisms of PV-driven cellular proliferation and carcinogenesis, co-factors associated with the development of HPV-associated cancers)
- HPV-induced cancers (anogenital cancer, head-and-neck cancers, non-melanoma skin cancer)
- Prospects and challenges on the currently available HPV vaccination programs, and next generation HPV vaccines (sustainability and mechanisms of long-term immunity, modelling of HPV evolution in post-vaccination era, global challenges in delivery of HPV vaccines, effect of pandemic settings and lockdowns on prevention of HPV-associated cancers)
Keywords: Papillomaviruses, immunity, tumour development
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