Highlights ► 1 in 10 women worldwide carries an HPV infection at any point in time. ► 610,000 incident cancers per annum are attributable to HPV infection globally. ► 80.6% of HPV associated cancers ...occur in less developed regions of the world. ► Cervix is the predominant HPV-associated cancer with 530,000 incident cases p.a. ► Genital warts are caused by HPV with an annual incidence of 0.1 to 0.2%.
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.
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.
Purpose
Human papilloma virus (HPV) infection is associated with several anogenital malignancies. Here, we set out to evaluate digital droplet PCR (ddPCR) as a tool for HPV 16, 18, 33 and 45 viral ...load quantification and, in addition, to compare the efficacy of the ddPCR assay for HPV 16 detection with that of quantitative real-time PCR (qPCR).
Methods
Clinical samples, positive for HPV genotypes 16, 18, 33 and 45 were analyzed for viral load using ddPCR. Sample DNA was cleaved before droplet generation and PCR. Droplets positive for VIC and FAM fluorescence were read in a QX200 Droplet reader™ (BIO-RAD) after which the viral load was calculated using Quantasoft software.
Results
We found that DNAs extracted from formalin fixed paraffin embedded (FFPE) tissue samples yielded lower amplification signals compared to those obtained from liquid based cytology (LBC) samples, but they were clearly distinguishable from negative background signals. The viral limit of detection was 1.6 copies of HPV 16, 2.8 copies of HPV 18, 4.6 copies of HPV 33 and 1.6 copies of HPV 45. The mean inter-assay coefficients of variability (CV) for the assays ranged from 3.4 to 7.0%, and the mean intra-assay CV from 2.6 to 8.2%. The viral load in the different cohorts of tumor samples ranged from 154 to 340,200 copies for HPV 16, 244 to 31,300 copies for HPV 18 and 738 to 69,100 copies for HPV 33. One sample positive for HPV 45 contained 1331 viral copies. When comparing qPCR data with ddPCR copy number data, the qPCR values were found to be 1 to 31 times higher.
Conclusions
Separation of fragments in nanodroplets may facilitate the amplification of fragmented human and viral DNA. The method of digital droplet PCR may, thus, provide a new and promising tool for evaluating the HPV viral load in clinical samples.
Purpose There has been increasing interest in understanding the natural history of HPV and the diseases that it causes in men. HPV infection is strongly associated with penile cancer, lack of ...neonatal circumcision and phimosis. We investigated the incidence of HPV infection in asymptomatic men and patients with phimosis. Materials and Methods We assessed 110 asymptomatic men and 30 patients who underwent circumcision due to phimosis. DNA was extracted from swabbed samples collected from asymptomatic men and from foreskin samples collected at circumcision. Polymerase chain reaction using consensus primers for detecting HPV-MY09/11 was performed to detect generic HPV DNA. HPV genotyping was done by polymerase chain reaction amplification with primers for the E6 gene DNA sequences HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV45 and HPV58. Results HPV was present in 46.66% of patients with phimosis, of whom 50% had high risk HPV genotypes. Of asymptomatic cases 16.36% were HPV positive but only 1 sample showed high risk HPV. We detected a significantly high rate of HPV genital infection in patients presenting with phimosis compared with asymptomatic men (p = 0.00167). The prevalence of high risk HPV genotypes in patients with phimosis was also statistically significant (p = 0.0004). Conclusions We found a robust association between phimosis and the genital HPV prevalence in men and a significant frequency of high risk HPV. Other studies are needed to investigate the occurrence of factors that can increase the incidence of penile carcinoma and determine its impact on female genital infection in cervical cancer.
Monitoring of condylomas is an early evidence of population effectiveness of human papillomavirus (HPV) vaccination programs. If reporting could include HPV typing, the contribution by vaccine HPV ...types to condyloma burden could be monitored.
A sentinel site for reporting of condyloma including HPV typing was established at the Centre for Sexual Health in Malmö, Sweden. In 2006 to 2009, when there were few HPV vaccines, 621 subjects with condyloma were reported and HPV genotyped.
Ninety-four percent of the condylomas contained genital HPV types. Thirty-five different genital HPV types were identified, with HPV6 (62%), HPV16 (13%), and HPV11 (10%) being the most common. At least 1 of the 4 HPV types in the HPV6/11/16/18 vaccine was detected in 77%. High-risk HPV types were more common in females (45%) than among males (27%) (odds ratio, 1.9; confidence interval, 1.3-2.8). Extended testing among subjects initially negative for HPV found 21 patients with cutaneous types of HPV, including a novel type (HPV153).
This report provides a baseline distribution of HPV types in condylomas before the introduction of an HPV vaccination program in this population. Human papillomavirus typing is feasible in routine condyloma reporting.
In order to lower the incidence of cervical cancer, vaccines against high-risk types of the human papilloma virus (hrHPV) were approved and brought on the market in 2007, with a partial reimbursement ...for Belgian citizens younger than 18 years old. Since 2010, a school-based vaccination program ensures a high vaccination coverage in young women. In this study, the impact of the Belgian vaccination program on the prevalence of HPV 16/18 is studied, together with the evolution of the prevalence of other hrHPV types and precancerous lesions.
Results of HPV typing and cytology in papanicolaou-smears from women aged 20-23 years taken between 2010 and 2019 were used. An older, nonvaccinated group of women of 40-45 years old served as a control group.
A significant decrease in prevalence of HPV types 16 and 18 was found in the 20-23-years-old women, whereas no decrease was found in the age group 40-45. Alongside this decrease, a significant decrease in prevalence of subtypes 6, 11 and 31 was observed, whereas type 31 is not included in the administered vaccines. Remarkably, there was no decrease in prevalence of cytological abnormalities in the study group during this study. There was even an increase in prevalence of high-risk types 53, 58 and 67.
These findings emphasise the need to maintain the screening programs, even in areas with high vaccination coverage.
•CRISPR/Cas12 and specific reporter sequence based lateral flow biosensor for nucleic acid detection were used.•A single copy of HPV DNA can be detected.•Results can be observed by naked eyes in less ...than an hour.•The Cas12a based strip can be used in diagnosis of infectious diseases.
Abnormal growth of uterine cervix cells may eventually lead to cervical cancer, which is mainly associated with the two most prevalent types of Human Papilloma Virus (HPV), namely HPV16 and HPV18. Cervical cancer can be prevented or treated owing to its slow progression. Therefore, its early, fast, and sensitive diagnosis is crucial. Herein, we developed an ultrasensitive approach for HPV16 and HPV18 detection based on a combination of loop-mediated isothermal amplification (LAMP), CRISPR-Cas12a trans-cleavage propensity and lateral flow biosensor (LFB), collectively termed CIALFB (CRISPR/Cas-Isothermal Amplification based LFB). CIALFB is characterized by Cas12a-mediated trans-cleavage of the reporter ssDNA upon target recognition, which results in undetectable LFB test line signal. This method was highly sensitive to detect 3.1 attomoles (∼1.8 copies) of the target, and reliably specific to detect both virus types from clinical samples with various HPV strains. Our system possesses the potential to detect other infectious diseases without tedious DNA extraction and handling, and expensive apparatuses.
There are no previous longitudinal studies on genotype-specific natural history of human papillomavirus (HPV) infections in oral mucosa of women.
In the Finnish Family HPV Study, 329 pregnant women ...were enrolled and followed up. HPV-genotyping of oral scrapings was performed with nested PCR and Multimetrix® test (Progen, Heidelberg, Germany). Incidence and clearance times and rates for each HPV-genotype identified in oral mucosa were determined. Predictors for incident and cleared HPV infections for species 7/9 genotypes were analyzed using Poisson regression model.
Altogether, 115 baseline HPV-negative women acquired incident oral HPV infection, and 79 women cleared their infection. HPV16 and multiple HPVs most frequently caused incident infections (65% and 12%) in 13.3 and 17.1 months respectively, followed by HPV58, HPV18 and HPV6 (close to 5% each) in 11-24 months. HPV58, HPV18 and HPV66 were the most common to clear. HPV6 and HPV11 had the shortest clearance times, 4.6 months and 2.5 months, and the highest clearance rates, 225.5/1000 wmr and 400/1000 wmr, respectively. The protective factors for incident oral HPV-species 7/9 infections were 1) new pregnancy during follow-up and 2) having the same sexual partner during FU. Increased clearance was related with older age and a history of atopic reactions, whereas previous sexually transmitted disease and new pregnancy were associated with decreased clearance.
HPV16 was the most frequent genotype to cause an incident oral HPV-infection. Low risk HPV genotypes cleared from oral mucosa more quickly than high risk HPV genotypes. Pregnancy affected the outcome of oral HPV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased adoption of HPV testing is expected in light of a growing global awareness of women's health and the recent launch of cervical cancer vaccines. Testing approaches must be both easy to ...implement, and offer intelligible representation of amplification results. Here, we introduce a simple, rapid, and visual HPV detection method based on a loop-mediated isothermal amplification (LAMP) assay. The visual LAMP assay can be successfully applied to amplify and differentiate the high-risk samples of HPV16 and HPV18, and results can be discriminated via the naked eye, without costly specialized apparatus. This HPV testing method has been evaluated with clinical samples and exhibited excellent reliability, as verified by polymerase chain reaction-microchip electrophoresis (PCR-MCE), and has a reduced false negative rate compared with cytological methods. The LAMP-based platforms with their facile operation and visual results possess great potential for on-site cervical cancer monitoring.
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•A simple, rapid, visualized LAMP assay was established for HPV detection.•Validation of the visual LAMP method.•The visual LAMP method exhibited the advantages of facile operation mode and intuitive result representation.•The visual LAMP method can be used in routine for high risk HPV detection.
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