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Introduction
Human papillomavirus (HPV) is a DNA virus from the papillomavirus family that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes. L1 is a major capsid protein of human papilloma virus. Infection with specific types of HPV has been associated with an increased risk of developing cervical neoplasia. Does not bind DNA.
Keywords
HPV 68 L1; HPV; HPV 68 VLP; HPV 68
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Background
Cervical cancer is the fourth most common cancer in the world, and human papillomavirus (HPV) has been linked to 99% of cervical cancers. In addition, HPV infections can also lead to anogenital cancers. The best way to prevent HPV is with a vaccine, and most current vaccine development is based on the major capsid protein L1, which contains specific epitopes recognized by the immune system. Genetic mutations in HPV L1 alter the epitopes recognized by antibodies, affecting vaccine efficacy. The International Agency for Research on Cancer (IARC) classifies HPV into 3 groups based on carcinogenicity, with types that cause cancer in humans in Group 1, types that probably cause cancer in humans in Group 2A, and types that may cause cancer in humans in Group 2B. There are no significant studies demonstrating a high risk of HPV68 causing cancer, so it is categorized as Group 2A. Ninety-six percent of cervical cancers are associated with one of the 13 HPV types in groups 1 and 2A. However, additional data are showing that HPV68, although rare, is more common in patients with cervical cancer than in women with normal cervical cytology, so the carcinogenicity classification system may be updated as findings change.
Figure 1. Phylogenetic classification among the major capsid proteins (L1) of multiple types (Source: Li Z, et al. 2018)
The major capsid L1 protein of HPV contains 12 β chains, 5 helices and 6 loops, which are located on the outer surface and contain highly variable immune dominant regions. The sequences are different in different HPV types. On the other hand, L1 protein contains a very conserved region. Because of its special conformational epitopes and its ability to self-assemble into virus-like particles (VLP), vaccines against HPV infection can be designed and developed. L1-VLP is an empty capsid formed by the pentamer of the main capsid L1 protein, which is similar to the original virion in morphology and antigenicity. They have a high degree of immunogenicity and induce congenital and acquired immune responses and produce high titers of neutralizing antibodies by providing the immune system with the same conformational epitopes as natural viruses. At the same time, because they do not contain viral DNA or carcinogenic proteins, they are not infectious and are safer to use. Different expression systems can produce L1-VLP, including insect cells, yeast systems and bacteria. These systems have been widely used in vaccine development.
Figure 2. A structural comparison of HPV L1s (Source: Li Z, et al. 2018)
Alternative Names
human papillomavirus 68 L1 HPV 68 L1 HPV type 68 L1
References
1. Li Z, et al. Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity. Nat Commun. 2018 Dec 18;9(1):5360.
2. Oumeslakht L, et al. Worldwide genetic variations in high-risk human papillomaviruses capsid L1 gene and their impact on vaccine efficiency. Gene. 2021 May 25;782:145533.
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References
Human papillomavirus genotype distribution in Ethiopia: an updated systematic review
Virol J
Authors: Derbie A, Mekonnen D, Nibret E, Maier M, Woldeamanuel Y, Abebe T.
Background: Cervical cancer is caused by infection with high-risk human papillomaviruses (HR-HPVs). It is one of the leading causes of cancer-related deaths in Ethiopia and globally. To develop efficient vaccination and HPV-based cervical cancer screening approaches, data on genotype distribution of HPVs is crucial. Hence, the study was aimed to review HPV genotype distribution in Ethiopia.
Methods: Research articles were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. Besides, Google Scholar was searched manually for grey literature. The last search was conducted on 18 August 2021. The first two authors independently appraised the studies for scientific quality and extracted the data using Excel sheet. The pooled HPV genotype distribution was presented with descriptive statistics.
Results: We have included ten studies that were reported from different parts of the country during 2005 and 2019. These studies included 3633 women presented with different kinds of cervical abnormalities, from whom 29 different HPV genotypes with a sum of 1926 sequences were reported. The proportion of high-risk, possible/probable high-risk and low-risk HPVs were at 1493 (77.5%), 182 (9.4%) and 195 (10.1%), respectively. Of the reported genotypes, the top five were HPV 16 (37.3%; 95% CI 35.2.1-39.5%), HPV 52 (6.8%; 95% CI 5.8-8.0%), HPV 35 (4.8%; 95% CI 3.9-5.8%), HPV 18 (4.4%; 95% CI 3.5-5.3%) and HPV 56 (3.9%: 95% CI 3.1-4.9%). Some of other HR-HPV groups include HPV 31 (3.8%), HPV 45 (3.5%), HPV 58 (3.1%), HPV 59(2.3%), and HPV 68 (2.3%). Among the high-risk types, the combined prevalence of HPV 16/18 was at 53.7% (95% CI 51.2-56.3%). HPV 11 (2.7%: 95% CI 2.1-3.5%), HPV 42 (2.1%: 95% CI 1.5-2.8%) and HPV 6 (2.1%: 95% CI 1.4-2.7%) were the most common low-risk HPV types.
Conclusions: We noted that the proportion of HR-HPV types was higher and HPV 16 in particular, but also HPV 52, HPV 35 and HPV 18, warrant special attention in Ethiopian's vaccination and HPV based cervical screening program. Additional data from other parts of the country where there is no previous HPV genotype report are needed to better map the national HPV genotypes distribution of Ethiopia.
A time-resolved fluorescence immunoassay for rapid and precise automatic quality control of human papillomavirus type 68 VLPs in human papillomavirus vaccine
J Immunol Methods
Authors: Li Z, Wu M, Chen Y, Li Y, Zhang Z, Zhai X, Cao Y, Li X, Yang Y, Wu Y, Lin G.
The effectiveness and necessity of human papillomavirus (HPV) vaccination to prevent HPV infection and cervical cancer are increasingly recognized by people. The 15-valent HPV vaccine, which protects against almost high-risk types of HPV viruses identified by WHO, has attracted much attention. However, as the valence of vaccines increases, quality control in the HPV vaccine production process is facing more challenges. The precise quality control of the HPV type 68 virus-like particles (VLPs), one of the unique components of the 15-valent HPV vaccine that distinguishes it from existing vaccines, is the new requirement for vaccine manufacturers. Here we developed a novel time-resolved fluorescence immunoassay (TRFIA) for rapid and precise automatic quality control of HPV68 VLPs in HPV vaccine. Two murine monoclonal antibodies specifically targeting the HPV68 L1 protein were used to establish a classical sandwich assay. Except for pretreating the vaccine sample, the whole analysis process was performed by a fully automated machine, which saves detection time and gets rid of manual error. Multiple experiments established that the current novel TRFIA can efficiently and reliably analyses HPV68 VLPs. Present novel TRFIA has exhibited merits with speed, robustness, high sensitivity with a minimum detection value of 0.08 ng/mL, considerable accuracy, a wide detection range (up to 1000 ng/mL) and excellent specificity. It is also expected to provide a new detection method for quality control for each HPV type VLPs. To summarize, the novel TRFIA is of great interest for application in HPV vaccine quality control.
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Figure 1. Phylogenetic classification among the major capsid proteins (L1) of multiple types
Figure 2. A structural comparison of HPV L1s
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