-
International Journal of Gynecological... Sep 2023Vulvar squamous cell cancer (VSC) accounts for 90% of vulvar cancers. Next-generation sequencing studies of VSC imply human papillomavirus (HPV) and p53 status play...
Vulvar squamous cell cancer (VSC) accounts for 90% of vulvar cancers. Next-generation sequencing studies of VSC imply human papillomavirus (HPV) and p53 status play separate roles in carcinogenesis and prognosis. We sought to describe the genomic landscape and analyze the immunologic profiles of VSC with respect to HPV and p53 status. A total of 443 VSC tumors underwent tumor profiling. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor samples. PD-L1, microsatellite instability were tested by fragment analysis, IHC, and next-generation sequencing. Tumor mutational burden-high was defined as >10 mutations per MB. HPV 16/18 positive (HPV+) status was determined using whole exome sequencing on 105 samples. Three cohorts were identified from 105 samples with known HPV: HPV+, HPV-/p53wt, and HPV-/p53mt. Where HPV and p53 status were examined, TP53 mutations were exclusive of HPV+ tumors. In all, 37% of samples were HPV+. Among the 66 HPV- tumors, 52 (78.8%) were HPV-/p53mt and 14 (21.2%) were HPV-/p53wt. The HPV-/p53wt cohort had a higher rate of mutations in the PI3KCA gene (42.9% HPV-/p53wt vs 26.3% HPV+ vs. 5.8% HPV-/p53mt, q =0.028) and alterations in the PI3K/AkT/mTOR pathway (57.1% HPV-/p53wt vs. 34.2% HPV+ vs. 7.7% HPV-/p53mt, q =0.0386) than the other 2 cohorts. Ninety-eight VSC tumors with HPV16/18 information underwent transcriptomic analysis and immune deconvolution method. No differences were observed in immune profiles. The HPV-/p53wt VSC tumors had significantly higher rates of mutations in the PI3KCA gene and alterations in the PI3K/AkT/mTOR pathway, a potential target that merits further investigation in this subgroup.
Topics: Female; Humans; Vulvar Neoplasms; Tumor Suppressor Protein p53; Human papillomavirus 16; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Human papillomavirus 18; Carcinoma, Squamous Cell; Genomics; Mutation; Papillomaviridae; Human Papillomavirus Viruses; TOR Serine-Threonine Kinases
PubMed: 37131274
DOI: 10.1097/PGP.0000000000000950 -
Duration of human papillomavirus persistence and its relationship with recurrent cervical dysplasia.European Journal of Cancer Prevention :... Nov 2023To evaluate how the duration of human papillomavirus (HPV) persistence influences the risk of developing recurrent high-grade cervical dysplasia (CIN2+).
OBJECTIVE
To evaluate how the duration of human papillomavirus (HPV) persistence influences the risk of developing recurrent high-grade cervical dysplasia (CIN2+).
METHODS
Data of patients with persistent HPV infection (at least at 6 months) after primary conization were extracted from a multi-institutional Italian database, retrospectively. Kaplan-Meier and Cox proportional hazards models were used to evaluate associations between duration of HPV persistence with the 5-year risk of developing recurrent CIN2+.
RESULTS
Overall, 545 patients met the inclusion criteria. Positive margins were detected in 160 (29.3%) patients. Overall, 247 (45.3%) and 123 (22.6%) patients had a documented infection from HPV16/18, and other high-risk HPV types. 187 (34.3%), 73 (13.4%), and 40 (7.3%) were diagnosed with persistent HPV infection at 12, 18, and 24 months, respectively. Patients with HPV persistence at 6 months experienced a risk of recurrence of 7.46%. Twelve-month HPV persistence strongly correlates with the risk of developing the recurrent disease (risk of recurrence: 13.1%). While, having HPV persistence >12 months did not correlate with an increased risk of recurrence (hazard ratio: 1.34 (95% confidence interval: 0.78-2.32); P = 0.336, log-rank test).
CONCLUSION
HPV persistence is one of the most important factors predicting the risk of CIN2+ recurrence. The risk of CIN2+ recurrence increased with the increase of HPV persistence for up to 1 year. The persistence of HPV after the first year does not appear as a risk factor.
Topics: Female; Humans; Human papillomavirus 16; Human papillomavirus 18; Human Papillomavirus Viruses; Neoplasm Recurrence, Local; Papillomaviridae; Papillomavirus Infections; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Multicenter Studies as Topic
PubMed: 37401466
DOI: 10.1097/CEJ.0000000000000822 -
Journal of Cancer Research and Clinical... Nov 2023Cervical cancer is a gynecological malignant tumor and a serious threat to women's health. Although human papillomavirus (HPV) infection and the occurrence of cervical... (Review)
Review
BACKGROUND
Cervical cancer is a gynecological malignant tumor and a serious threat to women's health. Although human papillomavirus (HPV) infection and the occurrence of cervical cancer are known to be closely related, the underlying carcinogenic mechanism of HPV is not fully understood. Extracellular vesicles (EVs) are found in a variety of body fluids and play an important role in both intercellular communication and cancer progression. Furthermore, the presence of EVs makes liquid biopsy of cervical cancer possible. The study of EVs in cervical cancer can provide clinical ideas for the diagnosis and treatment of the disease.
OBJECTIVES
The purpose of this article is to summarizes the role of EV contents in HPV-associated cervical cancer and discusses the possible clinical application of EVs in cervical cancer treatment.
METHODS
The search terms included the following: HPV with cervical cancer and extracellular vesicles. The initial literature search ended on March 1, 2023.
CONCLUSIONS
In HPV-positive cervical cancer, EV contents are changed due to the presence of HPV. HPV-positive cervical cancer affects the cell microenvironment and other surrounding cells through the secretion of EVs.
Topics: Humans; Female; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Extracellular Vesicles; Oncogene Proteins, Viral; Papillomaviridae; Tumor Microenvironment
PubMed: 37668793
DOI: 10.1007/s00432-023-05374-x -
Journal of the National Cancer Institute Feb 2024Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in...
BACKGROUND
Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown.
METHODS
We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status.
RESULTS
During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03).
CONCLUSION
This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Papillomavirus Infections; Papillomavirus Vaccines; Vaccination; Carcinoma in Situ; Squamous Intraepithelial Lesions; Precancerous Conditions; Human Papillomavirus Viruses; Papillomaviridae
PubMed: 37718496
DOI: 10.1093/jnci/djad189 -
Virchows Archiv : An International... Sep 2023The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous...
The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal neoplasms and on utility of p16 as a surrogate marker. p16 immunohistochemistry, HR-HPV mRNA ISH and quantitative real-time PCR (qPCR) were performed on a retrospective cohort of sinonasal papillomas and SCCs. KRAS mutation analysis was done in oncocytic papillomas. p16 positivity was present in 22/142 cases (15.5%) including eight inverted papillomas, one oncocytic papilloma (OP), and 13 SCC. Among these, mRNA ISH showed HR-HPV in the OP and two SCC, while another SCC was found to harbour HPV18 by qPCR. Two HPV-associated SCCs had foci of OP. mRNA ISH was negative in all p16 negative cases. p16 immunohistochemistry showed 68% concordance with mRNA ISH, and had sensitivity and negative predictive value of 100%; specificity was 67%, and positive predictive value was 14.3%. Association with HR-HPV in sinonasal papillomas and SCC is rare, and may be seen in cases demonstrating oncocytic morphology. p16 immunohistochemistry has low specificity and positive predictive value in low-prevalence populations; thus, reflex direct HR-HPV testing should be performed in p16 immunopositive cases. This two-step approach is viable in resource-limited settings, as the proportion of p16 positive cases is small.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Retrospective Studies; In Situ Hybridization; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Papilloma, Inverted; RNA, Messenger; Cyclin-Dependent Kinase Inhibitor p16; Papillomaviridae
PubMed: 37452847
DOI: 10.1007/s00428-023-03601-x -
The Oncologist Jun 2024Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these... (Review)
Review
Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis.
Topics: Humans; Papillomavirus Infections; Female; Male; Papillomaviridae; Neoplasms; Persistent Infection
PubMed: 38630576
DOI: 10.1093/oncolo/oyae071 -
Tumour Virus Research Dec 2023The incorporation of HPV DNA testing into cervical screening programs has shown that many HPV-positive women are cytologically normal, with HPV-positivity fluctuating... (Review)
Review
The incorporation of HPV DNA testing into cervical screening programs has shown that many HPV-positive women are cytologically normal, with HPV-positivity fluctuating throughout life. Such results suggest that papillomaviruses may persist in a latent state after disease clearance, with sporadic recurrence. It appears that virus latency represents a narrow slot in a wider spectrum of subclinical and possibly productive infections. Clinical studies, and animal model infection studies, suggested a key role for host immune surveillance in maintaining such asymptomatic infections, and although infections may also be cleared, most studies have used the term 'clearance' to describe a situation where the presence of HPV DNA falls below the clinical detection level. Given our knowledge of papillomavirus immune evasion strategies and the restricted pattern of viral gene expression required for 'basal cell' persistence, the term 'apparent clearance' and 'subclinical persistence' of infection may better summarise our understanding. Subclinical infection also encompasses the lag phase, which occurs between infection and lesion development. This is dependent on infection titre, with multifocal infections developing more rapidly to disease. These concepts can usefully influence patient management where HPV-positivity occurs sometime after the onset of sexual activity, and where vertical transmission is suspected despite a lag period.
Topics: Animals; Humans; Female; Papillomavirus Infections; Human Papillomavirus Viruses; Uterine Cervical Neoplasms; Asymptomatic Infections; Early Detection of Cancer; Papillomaviridae; DNA
PubMed: 37354969
DOI: 10.1016/j.tvr.2023.200268 -
American Journal of Obstetrics and... Jun 2024In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2...
BACKGROUND
In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression.
OBJECTIVE
This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.
STUDY DESIGN
We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF-DEIA-LiPA system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model.
RESULTS
A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups.
CONCLUSION
The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.
Topics: Humans; Female; Uterine Cervical Dysplasia; Adult; Disease Progression; Uterine Cervical Neoplasms; Papillomavirus Infections; Young Adult; Genotype; Cohort Studies; Neoplasm Grading; Papillomaviridae; Watchful Waiting; Human papillomavirus 16; Denmark; Human Papillomavirus Viruses
PubMed: 38336125
DOI: 10.1016/j.ajog.2024.01.029 -
Journal of Medical Virology Oct 2023Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in... (Meta-Analysis)
Meta-Analysis
Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.
Topics: Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; Papillomaviridae; Uterine Cervical Neoplasms; Adenocarcinoma; Genotype
PubMed: 37861377
DOI: 10.1002/jmv.29190 -
Equine Veterinary Journal Jan 2024Papillomaviruses 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...
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.
OBJECTIVES
To describe a novel equid papillomavirus detected in oral swab samples collected from donkeys (Equus asinus) found on the Northwest plateau of China.
STUDY DESIGN
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.
MAIN LIMITATIONS
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.
Topics: Horses; Animals; Humans; Equidae; Phylogeny; Cross-Sectional Studies; Genome, Viral; Papillomaviridae
PubMed: 37246448
DOI: 10.1111/evj.13957