Background
Human papillomaviruses (HPVs) are a group of small, envelope-less DNA viruses, 52-55 nm in diameter, a population that includes more than 450 genotypes (types) with more than 10% DNA sequence variation in the most conserved L1 open reading frames (ORFs). HPV infections can lead to benign tumors or cancers. HPV can be classified into low-risk and high-risk types based on their relevance to cancer, with HPV16 and HPV18 being the two most common high-risk HPVs, and about 70% of all HPV-related cervical and head and neck cancers are caused by HPV 16 and HPV 18. Different from low-risk HPV, high-risk HPV expresses two powerful oncoproteins E6 and E7, which mediate the degradation of p53 and pRb (two tumor suppressor proteins essential for cell cycle control and genomic stability), respectively, leading to HPV-induced carcinogenesis. HPV 16 and HPV 18 are associated with 70% of moderate cervical intraepithelial neoplasia (CIN 2 or higher). HPV 16 accounts for 87% of squamous carcinomas, while HPV 18 accounts for 86% of adenocarcinomas.
Papillomavirus contains a double-stranded circular DNA genome about the size of 8kb. All papillomavirus genomes can be divided into three distinct regions: upstream regulatory region (URR), early (E) and late (L) gene regions by two polyadenylated (pA) signals, namely, early (pAE) and late (pAL). The URR region does not encode any protein, also known as the long control region (LCR). The URR of different papillomaviruses varies in size, and HPV 16 is 853bp. HPV URR contains binding sites of viral E1 and E2 proteins that initiate HPV replication, as well as several cellular transcription factors used to initiate transcription, including NFI, Oct-1 (OCT), AP-1, TEF-1 (TF1) and SP1. URR also contains a replication source (Ori) that is essential for papillomavirus replication, which is highly homologous to mammalian autonomous replication conserved sequence (ACS).
Figure 1. Genome structure of HPV 16
(Source: Yu L, et al. 2022)
To initiate viral infection, the L1 capsid protein binds to heparan sulfate proteoglycans (HSPGs) located on the surface of epithelial cells or basement membranes, or interacts with laminin-332 on the extracellular matrix, and upon binding, the viral capsid undergoes a conformational modification mediated by cyclophilin (CyP) B, ultimately exposing the minor capsid protein L2. The HPV 16 gene encoding L1 capsid protein lies between 5559 and 7154 nucleotides, with a size of 531 amino acids. The L1 sequence similarity between the HPV 16 mutant and the virus genome reference sequence is more than 98%. It is worth noting that the non-synonymous mutation of the L1 gene is located near the neutralizing epitope, increasing the probability of evading immune response. The current design of HPV vaccines is based on virus-like particles (VLP), which are produced by the major capsid protein L1 and mimic the structure of virions. Vaccination of HPV vaccine can produce high quality and long-term antibody titers, most of which are immunoglobulins (IgG) specific to the corresponding HPV L1 proteins. Creative Diagnostics is here to provide you with HPV 16 L1-capsids IgG ELISA kit that can qualitatively detect the IgG concentration of HPV 16 L1 capsid protein in human serum and plasma.
Alternative Names
Human papillomavirus type 16 L1-capsids IgG ELISA
Human papillomavirus 16 L1-capsids IgG ELISA
HPV 16 L1-capsids IgG ELISA
References
- 1. Bletsa G, et al. Genetic variability of the HPV16 early genes and LCR. Present and future perspectives. Expert Rev Mol Med. 2021 Dec 1;23:e19.
- 2. Yu L, et al. HPV16 and HPV18 Genome Structure, Expression, and Post-Transcriptional Regulation. Int J Mol Sci. 2022 Apr 29;23(9):4943.
References
Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
Nat Commun
Authors: edard MC, Chihanga T, Carlile A, Jackson R, Brusadelli MG, Lee D, VonHandorf A, Rochman M, Dexheimer PJ, Chalmers J, Nuovo G, Lehn M, Williams DEJ, Kulkarni A, Carey M, Jackson A, Billingsley C, Tang A, Zender C, Patil Y, Wise-Draper TM, Herzog TJ, Ferris RL, Kendler A, Aronow BJ, Kofron M, Rothenberg ME, Weirauch MT, Van Doorslaer K, Wikenheiser-Brokamp KA, Lambert PF, Adam M, Steven Potter S, Wells SI.
Abstract
Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle is dependent on the differentiation program of stratified squamous epithelium, but the landscape of keratinocyte subpopulations which support distinct phases of the viral life cycle has yet to be elucidated. Here, single cell RNA sequencing of HPV16 infected compared to uninfected organoids identifies twelve distinct keratinocyte populations, with a subset mapped to reconstruct their respective 3D geography in stratified squamous epithelium. Instead of conventional terminally differentiated cells, an HPV-reprogrammed keratinocyte subpopulation (HIDDEN cells) forms the surface compartment and requires overexpression of the ELF3/ESE-1 transcription factor. HIDDEN cells are detected throughout stages of human carcinogenesis including primary human cervical intraepithelial neoplasias and HPV positive head and neck cancers, and a possible role in promoting viral carcinogenesis is supported by TCGA analyses. Single cell transcriptome information on HPV-infected versus uninfected epithelium will enable broader studies of the role of individual keratinocyte subpopulations in tumor virus infection and cancer evolution.
The combined HPV16-E2/E6/E7 T cell response in oropharyngeal cancer predicts superior survival
Cell Rep Med
Authors: Santegoets SJ, Stolk A, Welters MJP, van der Burg SH.
Abstract
Tumor-infiltrating HPV16-E2-specific CD8+ T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4+ T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16+ OPSCC cohort, we regularly detect HPV16-E2-specific CD4+ and CD8+ intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.