A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Potent anti-tumor T cell response and efficient intratumoral T cell infiltration are the major challenges for therapeutic cancer vaccines. To address these issues, a nano-vaccine system has been designed to promote anti-tumor T cell responses, and intratumoral infiltration was examined in various murine tumor models. Subcutaneous vaccination with nanodiscs carrying human papillomavirus (HPV)-16 E7 antigen elicits as high as ~32% E7-specific CD8 α + T cell responses in circulation, representing a 29-fold improvement over the soluble peptide vaccination. Importantly, nanodisc vaccination also promotes robust intratumoral T cell infiltration and eliminates HPV16 E6/E7-expressing TC-1 tumors at mucosal sites, including lungs, inner lip, and intravaginal tissues. In a benchmark study with a live Listeria vaccine combined with anti-PD-1 IgG, nanodiscs plus anti-PD-1 immune checkpoint blockade elicits comparable levels of T cell responses with anti-tumor efficacy. Furthermore, compared with Complete Freund\'s Adjuvant combined with tetanus toxoid, nanodisc vaccination in HLA-A02 mice generates >200-fold stronger IFN-γ+ T cell responses against a neoantigen from an HLA-A02 melanoma patient. Overall, these results show that the nanodisc system is a promising cancer vaccine platform for inducing anti-tumor T cell responses.

BACKGROUND: Papillomaviruses can be of great medical importance as they infect humans and animals such as Equus species, other livestock and pets. They are responsible for several papillomas and benign tumours in their host.
OBJECTIVE: To describe a novel equid papillomavirus detected in oral swab samples collected from donkeys (Equus asinus) found on the Northwest plateau of China.
METHODS: Cross-sectional.
METHODS: Swab samples collected from the oral mucosa of 32 donkeys in the Gansu Province of China, were subjected to viral metagenomic analysis to detect the presence of Papillomavirus. After de novo assembly, a novel papillomavirus genome designated as Equus asinus papillomavirus 3 (EaPV3) was identified in the studied samples. Additional bioinformatic analysis of the assembled genome was done using the Geneious prime software (version 2022.0.2).
RESULTS: The complete circular genome of EaPV3 is 7430 bp in length with a GC content of 50.8%. The genome was predicted to contain five ORFs coding for three early proteins (E7, E1, and E2) and two late proteins (L1 and L2). Phylogenic analysis of the nucleotide sequences of the concatenated amino acid sequences of the E1E2L1L2 genes revealed that EaPV3 is most closely related to Equus asinus papillomavirus 1 (EaPV1). The genome analysis of EaPV3 revealed similar genome organisation with other equine papillomavirus and the presence of E7 papillomavirus oncoprotein.
CONCLUSIONS: Since there were no warts in the oral cavity of the donkeys in this study, and no biopsy samples taken, we are unable to conclusively link the novel virus to any clinical condition in the donkeys.
CONCLUSIONS: The Comparative characterisation of EaPV3 and its closest relatives, as well as phylogenetic analysis demonstrated that it is a novel virus specie that clusters within the Dyochipapilloma PV genus.
UNASSIGNED: O papilomavírus pode apresentar uma importância médica significante por poder infectar humanos e animais, incluindo animais da espécie Equus, animais de produção e animais domésticos. Esse vírus é responsável por vários papilomas e tumores benignos em seus hospedeiros.
OBJECTIVE: Descrever um novo papilomavírus detectado em amostras de swab oral coletados de Equus asinus no Noroeste da China.
UNASSIGNED: Estudo transversal.
METHODS: Amostras de swab coletadas da mucosa oral de 32 jumentos da província de Gansu na China foram submetidos para análise metagenômica viral para detectar a presença de papilomavírus. Após a montagem de novo, um novo papilomavírus, denominado Equus asinus papilomavírus 3 (EaPV3), foi identificado nas amostras estudadas. Análise bioinformática adicional foi realizada para montar o genoma desse vírus usando o Geneious prime software (version 2022.0.2).
RESULTS: O genoma circular completo do EaPV3 possui 7.430 bp, e apresenta 50.8% de conteúdo GC. Foi previsto que o genoma possui cinco codificações ORFs para três proteínas precoces (E7, E1 e E2) e duas proteínas retardas (L1 2 L2). Análise filogenética da sequência de nucleotídeos dos genes E1E2L1L2 dos amino ácidos concatenados revelaram que o EaPV3 é bastante similar aos EaPV1. A análise genômica do EaPV3 revelou uma organização genômica similar com outros papilomavírus equinos e a presença da oncoproteína E7. PRINCIPAIS LIMITAÇÕES: Como não havia nenhuma verruga na cavidade oral dos jumentos investigados neste estudo, e nenhuma biópsia foi realizada, não é possível concluir uma associação entre este novo vírus e qualquer condição clínica em jumentos. CONCLUSÕES: A caracterização comparativa do EaPV3 com outros vírus similares e a análise filogenética demonstraram que este é um novo vírus que assemelha-se com os papilomavírus do gene Dyochipapilloma.

Here, using viral metagenomic method, a novel whale papillomavirus (temporarily named wPV, GenBank accession number OP856597) was discovered in a whale (Delphinapterus leucas) pharyngeal metagenomic library. The complete genome size of wPV is 7179 bp, with GC content of 54.4% and a nucleotide composition of 23.4% A, 22.3% T, 28.4% G, and 25.9% C. The viral genome has a typical papillomavirus organization pattern, and five ORFs were predicted, including two late genes encoding L1 and L2, and three early genes encoding E1, E2, and E6. Pairwise sequence comparison and phylogenetic analysis based on the L1 gene sequence indicated that wPV may be a novel species within genus Dyodeltapapillomavirus. In addition, the E2 region of wPV was predicted to have a potential recombination event. The discovery of this novel papillomavirus increases our understanding of the viral ecology of marine mammals, providing insights into possible future infectious diseases.

UNASSIGNED: Human papillomavirus (HPV) type-specific strategies play a key role in the prevention of cervical intraepithelial neoplasia (CIN), but evidence on the HPV type-specific prevalence in CIN is limited.
UNASSIGNED: This multicentric study estimates the prevalence of high-risk HPV types in CIN cases and the associations of HPV infection patterns with high-grade CIN in China in 2017-2018.
UNASSIGNED: Population-based prevention strategies should give preference to HPV-16 and 18, and strategies for non-16/18 high-risk HPV are essential for the elimination of cervical cancer.

Viruses are important components of the human body. Growing evidence suggests that they are engaged in the physiology and disease status of the host. Even though the vaginal microbiome is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, little is known about the role of the vaginal virome. In this pilot exploratory study, using unbiased viral metagenomics, we aim to investigate the vaginal eukaryotic virome in women with different levels of cervical lesions, and examine their associations with different cervical disease status. An altered eukaryotic virome was observed in women with different levels of lesions and Lactobacillus profiles. Anelloviruses and papillomaviruses are the most commonly detected eukaryotic viruses of the vaginal virome. Higher abundance and richness of anelloviruses and papillomaviruses were associated with low-grade squamous intraepithelial lesion (LSIL) and CC. Besides, higher anellovirus abundance was also associated with lactobacillus-depleted microbiome profiles and bacterial community state (CST) type IV. Furthermore, increased correlations between Anelloviridae and Papillomaviridae occurred in the women with increased cervical disease severity level from LSIL to CC. These data suggest underlying interactions between different microbes as well as the host physiology. Higher abundance and diversity of both anelloviruses and papillomaviruses shared by LSIL and CC suggest that anellovirus may be used as a potential adjunct biomarker to predict the risk of HPV persistent infection and/or CC. Future studies need to focus on the clinical relevance of anellovirus abundance with cervical disease status, and the evaluation of their potential as a new adjunct biomarker for the prediction and prognoses of CC.

Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral-host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.

The goal of this study was to identify human papillomavirus (HPV) type 52 genetic and epigenetic changes associated with high-grade cervical precancer and cancer. Patients were selected from the HPV Persistence and Progression (PaP) cohort, a cervical cancer screening program at Kaiser Permanente Northern California (KPNC). We performed a nested case-control study of 89 HPV52-positive women, including 50 cases with predominantly cervical intraepithelial neoplasia grade 3 (CIN3) and 39 controls without evidence of abnormalities. We conducted methylation analyses using Illumina sequencing and viral whole genome Sanger sequencing. Of the 24 CpG sites examined, increased methylation at CpG site 5615 in HPV52 L1 region was the most significantly associated with CIN3, with a difference in median methylation of 17.9% (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.9-11.8) and an area under the curve of 0.73 (AUC; 95% CI = 0.62-0.83). Complete genomic sequencing of HPV52 isolates revealed associations between SNPs present in sublineage C2 and a higher risk of CIN3, with ORs ranging from 2.8 to 3.3. This study identified genetic and epigenetic HPV52 variants associated with high risk for cervical precancer, improving the potential for early diagnosis of cervical neoplasia caused by HPV52.

Objective: To evaluate the value of p16INK4a detected by p16INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods: Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16INK4a technology, among them, 902 cases were offered p16INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16INK4a staining. Participants with complete LCT examination, HR-HPV test, p16INK4a staining and histopathological examination results were included in this study. The performance of p16INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+] were analyzed. Results: (1) One-thousand and ninety-seven cases with complete data of p16INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ)+ and 34 cases of HSIL (CIN Ⅲ)+ were detected. The positive rate of p16INK4a in HSIL (CIN Ⅱ)+ was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16INK4a as primary screening for HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16INK4a for detecting HSIL (CIN Ⅱ)+ or HSIL (CIN Ⅲ)+ were higher than that of LCT alone or adjunctive HR-HPV (P<0.01), while the sensitivity were similar (P>0.05). (4) p16INK4a staining as secondary screening: p16INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions: For primary screening, p16INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.
目的： 探讨p16INK4a免疫细胞化学染色（p16INK4a染色）作为新一代子宫颈细胞学检查技术在人群子宫颈癌初筛与辅助常规细胞学检查及高危型（HR）-HPV初筛后的二次筛查中的价值。 方法： 募集2016—2018年深圳及周边地区25~65岁有性生活的非妊娠期妇女5 747例，采用HR-HPV联合子宫颈液基细胞学检查（LCT）进行子宫颈癌初筛；并行p16INK4a染色，其中902例在初筛的同时进行p16INK4a染色，其余4 845例为HR-HPV与LCT初筛阳性回叫行阴道镜检查时取样进行p16INK4a染色。将具有完整LCT检查、HR-HPV检测、p16INK4a染色及子宫颈活检后病理诊断结果者纳入本研究。以组织学病理诊断为“金标准”，评价p16INK4a染色作为子宫颈癌初筛、辅助LCT检查及HR-HPV初筛后的二次分流方案检出子宫颈病变［即高级别鳞状上皮内病变（HSIL）］，包括HSIL［子宫颈上皮内瘤变（CIN）Ⅱ］及以上级别病变［HSIL（CIN Ⅱ）+］、HSIL（CIN Ⅲ）及以上级别病变［HSIL（CIN Ⅲ）+］的筛查效率。 结果： （1）具有完整LCT检查、HR-HPV检测、p16INK4a染色及子宫颈活检病理诊断结果者共1 097例，纳入本研究。病理诊断：正常子宫颈995例，低级别鳞状上内病变（LSIL）37例、HSIL 64例及子宫颈癌1例，其中HSIL（CIN Ⅱ）+ 65例，HSIL（CIN Ⅲ）+ 34例。HSIL（CIN Ⅱ）+患者的p16INK4a阳性率（89.2%，58/65）显著高于CINⅠ或正常子宫颈者（10.2%，105/1 032；P<0.01）。（2）p16INK4a染色作为初筛方案：与HR-HPV检测比较，p16INK4a染色检出HSIL（CIN Ⅱ）+、HSIL（CIN Ⅲ）+的敏感度均无显著差异（95.4%与89.2%，94.1%与94.1%；P>0.05），但其特异度均显著增高（82.5%与89.8%，80.2%与87.7%；P<0.05）；而与LCT结果≥LSIL比较，p16INK4a染色检出HSIL（CIN Ⅱ）+、HSIL（CIN Ⅲ）+的敏感度、特异度均无显著差异（P>0.05）。（3）p16INK4a染色辅助LCT检查：与单独LCT检查或HR-HPV检测辅助LCT检查比较，p16INK4a染色辅助LCT检查检出HSIL（CIN Ⅱ）+、HSIL（CIN Ⅲ）+的特异度均显著增高（P<0.01），而敏感度均无显著差异（P>0.05）。（4）p16INK4a染色作为二次分流方案：HR-HPV初筛后以p16INK4a阳性作为二次分流指标与LCT结果≥ASCUS作为二次分流指标比较，检出HSIL（CIN Ⅱ）+、HSIL（CIN Ⅲ）+的敏感度均无显著差异（84.6%与90.8%，88.2%与91.2%；P>0.05），而特异度均有显著差异（94.1%与89.7%，91.9%与87.4%；P<0.01）；作为二次分流方案，HPV 16和（或）18型（HPV 16/18型）阳性与p16INK4a阳性序贯的方案，HPV 16/18型阳性与LCT结果≥ASCUS序贯的方案，两种方案比较，检出HSIL（CIN Ⅲ）+的敏感度无显著差异（分别为88.2%、94.1%，P=0.500），而前者的特异度显著增高（分别为88.3%、83.0%，P<0.01），且前者的阴道镜转诊率显著降低（分别为14.0%、19.4%，P=0.005）。 结论： p16INK4a染色作为子宫颈癌初筛方案检出子宫颈病变的敏感度与HR-HPV检测相当、特异度与LCT检查相当；且在HR-HPV阳性患者的二次分流中具有优势，并可辅助LCT检查进行诊断分级，提高了子宫颈细胞学筛查的准确率。.