OBJECTIVES: Human papillomavirus (HPV) infections are highly prevalent sexually transmitted infections, notably associated with various cancers. This study analyses the health and economic impacts of HPV-associated diseases in the Czech Republic and evaluates the cost-effectiveness of a catch-up vaccination program. METHODS: Utilizing a Markov multistate model, the study assesses the lifetime impacts and costs related to HPV infections. Cohorts of ages 15-21 were simulated to assess the impact of catch-up vaccination outside the 11-year-old age group. RESULTS: The total quality-adjusted life years (QALYs) for the female and male cohorts (together 119,362 individuals) were higher in the vaccination scenario compared to the non-vaccination scenario. The increase in QALYs was 122,246 and 200,852 respectively, when considering the actual vaccination rates. Across both cohorts, 329 cancer-related deaths were prevented. In the probabilistic sensitivity analysis for the female population, vaccination was the dominant strategy in 99.3% of iterations. In the male population, vaccination was the dominant strategy in 80.3% of iterations. The implementation of catch-up vaccination for the 15-21 age group significantly increased QALY gains and reduced life-years-lost (LYLs). In the female cohort, all analysed rates of catch-up vaccination were the dominant strategy, while in the male cohort, the incremental cost-effectiveness ratios (ICERs) remained consistently below 42,000 CZK/QALY. CONCLUSIONS: The catch-up vaccination program for 15-21-year-olds is cost-effective and can prevent a significant number of HPV-related cancers in both men and women.

• Klíčová slova
• Cost effectiveness, Human papillomavirus, QALYs, Vaccination program,
• MeSH
• analýza nákladové efektivity MeSH
• analýza nákladů a výnosů MeSH
• dospělí MeSH
• infekce papilomavirem * prevence a kontrola   ekonomika   epidemiologie   MeSH
• kvalitativně upravené roky života MeSH
• lidé MeSH
• Markovovy řetězce MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory děložního čípku prevence a kontrola   ekonomika   MeSH
• osobní újma zaviněná nemocí * MeSH
• vakcíny proti papilomavirům * ekonomika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• vakcíny proti papilomavirům * MeSH

The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia. Both vaccines have proven to be highly protective in people. HPV pseudovirions are assembled in HEK293TT cells from matched L1 and L2 capsid proteins to encapsidate a reporter gene. Pseudovirions and genuine virions have structural differences and they infect cell lines or primary human keratinocytes (PHKs) with different efficiencies. In this study, we show that sera and isolated IgG from women immunized with Gardasil prevent authentic HPV-18 virions from infecting PHKs, whereas non-immune sera and purified IgG thereof are uniformly ineffective. Using early passage PHKs, neutralization is achieved only if immune sera are added within 2-4h of infection. We attribute the timing effect to a conformational change in HPV virions, thought to occur upon initial binding to heparan sulfate proteoglycans (HSPG) on the cell surface. This interpretation is consistent with the inability of immune IgG bound to or taken up by PHKs to neutralize the virus. Interestingly, the window of neutralization increases to 12-16h in slow growing, late passage PHKs, suggestive of altered cell surface molecules. In vivo, this window might be further lengthened by the time required to activate the normally quiescent basal cells to become susceptible to infection. Our observations help explain the high efficacy of HPV vaccines.

• Klíčová slova
• FcRn, HPV antibodies, HPV vaccine, HPV-18 neutralization, Primary human keratinocytes,
• MeSH
• antisérum imunologie   MeSH
• heparansulfát proteoglykany metabolismus   MeSH
• imunoglobulin G krev   imunologie   MeSH
• infekce papilomavirem prevence a kontrola   MeSH
• keratinocyty virologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lidský papilomavirus 18 MeSH
• neutralizační testy MeSH
• neutralizující protilátky krev   imunologie   MeSH
• protilátky virové krev   imunologie   MeSH
• rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antisérum MeSH
• heparansulfát proteoglykany MeSH
• imunoglobulin G MeSH
• neutralizující protilátky MeSH
• protilátky virové MeSH
• rekombinantní kvadrivalentní vakcína proti lidskému papilomaviru typu 6, 11, 16, 18 MeSH

UNLABELLED: Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B. IMPORTANCE: This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.

• MeSH
• fylogeneze MeSH
• genetická variace * MeSH
• genom virový * MeSH
• genomika MeSH
• genotyp MeSH
• infekce papilomavirem virologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• lidský papilomavirus 11 klasifikace   genetika   izolace a purifikace   MeSH
• molekulární evoluce MeSH
• otevřené čtecí rámce MeSH
• pravděpodobnostní funkce MeSH
• sekvenční seřazení MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH