Detection Of Human Papillomavirus DNA Research Articles

HPV Detection on Lung Interstitium Through Bronchoalveolar Lavage (BAL) in Patients from City Recife, Pernambuco-Brazil

Bronchoalveolar lavage (BAL) is a non-invasive tool that allows direct sampling of the lung interstitium, facilitating cytological, microbiological, and molecular analyses. The Human Papillomavirus (HPV), known for its oncogenic role mainly in the genital regions, also can be found in the lungs, but its pathological implications remain poorly elucidated. This study aims to identify the presence of HPV-DNA in patients with suspected lung diseases through BAL. A cross-sectional and analytical study was carried out involving 146 patients admitted to hospitals in the Metropolitan Region of Recife. To detect HPV DNA, 46 samples were processed using PCR technique with MY09/11 consensus primers, followed by Nested-PCR with GP5/6 primers. The presence of HPV-DNA was confirmed in 4 (8.69%) samples, all benign and suspected of interstitial diseases. These findings indicate the feasibility of detecting HPV in the lung interstitium by BAL using Nested-PCR and suggest a new perspective in understanding the presence of HPV in lung tissue. In addition, to corroborating the statement that HPV is not limited to tissue and malignant samples, offering a new methodological dimension to the HPV investigation on lung.

Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022.

The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41-50 and 51-60 years old, and finally, 44% of subjects were >60 years old. Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism.

Integration between the Papanicolaou smear test and detection of human papillomavirus DNA suggests the need to update the screening strategy for the prevention of cervical uterine cancer

Integration between the Papanicolaou smear test and detection of human papillomavirus DNA suggests the need to update the screening strategy for the prevention of cervical uterine cancer

Human Papillomavirus Is Rare and Does Not Correlate with p16INK4A Expression in Non-Small-Cell Lung Cancer in a Jordanian Subpopulation.

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Analysis of the application value of HPV mRNA and DNA detection in early screening of cervical lesions

Aim: At present, COBAS human papillomavirus (HPV) and Aptima HPV screening are widely used to detect HPV infection. In this study, we compared and analyzed the positive rates of DNA and mRNA (n = 10,128 women). Methods: After HPV screening, colposcopy was performed. Subsequently, pathological analysis was conducted on the screening results. Results: In Aptima HPV 16 group, the proportion of pathological lesions ≥CIN2 was 32.69%, while in COBAS HPV group, it was 24.18% (p < 0.05). Aptima HPV other risk types and COBAS HPV other risk types, the proportion of cases ≥CIN2 was 12.42 and 5.79%, respectively (p < 0.001). Conclusion: The results illustrated that the Aptima HPV test detects more accurately clinically relevant lesions than the COBAS test.

Naturally developed HPV16 antibodies and risk of newly detected cervical HPV infection outcomes.

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections.

Menstrual Blood as a Diagnostic Specimen for Human Papillomavirus Genotyping and Genital Tract Infection Using Next-Generation Sequencing as a Novel Diagnostic Tool.

Menstrual blood (MB) is a convenient specimen type that can be self-collected easily and non-invasively by women. This study assessed the potential application of MB as a diagnostic specimen to detect genital tract infections (GTIs) and human papillomavirus (HPV) infections in women. Genomic DNA was extracted from MB samples. Pacific Bioscience (Pacbio) 16S ribosomal DNA (rDNA) high-fidelity (HiFi) long-read sequencing and HPV PCR were performed. MB samples were collected from women with a pathological diagnosis of CIN1, CIN2, CIN3 or HPV infection. The sensitivity and positive predictive value (PPV) of high-risk HPV detection using MB were found to be 66.7%. A shift in vaginal flora and a significant depletion in Lactobacillus spp. in the vaginal microbiota communities were observed in the MB samples using 16S rDNA sequencing. In this study, we demonstrated that MB is a proper diagnostic specimen of consideration for non-invasive detection of HPV DNA and genotyping using PCR and the diagnosis of GTIs using metagenomic next-generation sequencing (mNGS). MB testing is suitable for all women who menstruate and this study has opened up the possibility of the use of MB as a diagnostic specimen to maintain women's health.

Human papillomavirus Detection Rates in Bowen's Disease: Correlation with Pelvic and Digital Region Involvement and Specific p53 Immunostaining Patterns.

The relationship between human papillomavirus (HPV) and Bowen's disease (BD) is not fully understood. To investigate the differences in HPV detection rates in BD samples across various body regions and analyze the expression patterns of p53, p16, and Ki-67 in relation to HPV presence. Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53, and Ki-67 was performed. Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (69.2%, P<0.001) and digital (50.0%, P=0.022) areas compared to those in the other regions. HPV presence was significantly correlated with p53 negativity (P=0.002), the p53 "non-overexpression" IHC pattern (P<0.001), and p53-p16 immunostain pattern discordance (P<0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern, or Ki-67 expression. Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in pathogenesis of BD in the pelvic and digital regions.

Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: Amulticentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

Prevalence and significance of HPV DNA detection below the clinical threshold of the commercial kit Alinity m HR-HPV assay (Abbott).

The positive clinical threshold of human papillomavirus(HPV) tests validated for primary cervical cancer screening (CCS) is designed to offer an optimal balance between clinical sensitivity and specificity. However, there may be a gap between the analytical sensitivity of the test and the positive clinical threshold, referred to here as the "gray-zone."This study aims to determine the prevalence and significance of HPV results obtained in the gray-zone in routine practice. Cervical samples obtained in our institution for CCS over a 22-month-period were tested with the Alinity m HR-HPV Assay (Abbott). Clinical and biological data, including cytological results and patients' HPV history were collected. Of the 6101 samples collected, 1.7% had an HPV result in the gray-zone (102 patients). The proportion of gray-zone results varied according to HPV genotype, reaching 11.8% of samples with detectable HPV DNA in the case of HPV31/33/52/58 genotypes. Reflex cytologies showed no abnormalities or AtypicalSquamous Cells of Undetermined Significance results in 74.6% and 17.9% of cases, respectively. A previous or subsequent HPV-positive result with a (possibly) identical genotype was observed in 58% and 38% of cases, respectively. Two women with a history of persistent HPV detection had a CIN2+ lesion 1 year after the gray-zone result. In conclusion, the proportion of HPV results in the gray-zone varies according to genotype. No cytological abnormality is observed in the majority of cases, but a few rare patients with a history of persistent HPV infection should be closely monitored even if the HPV result is transiently located in the gray-zone.

Detection of Multiple HPV Types in Liquid Biopsies of Cervical Neoplasia.

More than 95% of cervical cancers and their precancerous lesions are caused by human papillomavirus (HPV). Cell-free (cf) HPV DNA detection in blood samples may serve as a monitoring tool for cervical cancer. In our methodological study, an HPV panel for simultaneous detection of 24 types using mass spectrometry-based analysis was developed for liquid biopsy approaches and tested on HPV positive cell lines, plasmid controls, and cervical high-grade squamous intraepithelial lesions (HSIL) in positive smear samples (n = 52). It was validated in cfDNA blood samples (n = 40) of cervical cancer patients. The HPV panel showed proficient results in cell lines and viral plasmids with a limit of detection of 1 IU (international units)/µL for HPV16/18 and 10GE/µL for HPV11/31/33/39/45/51/52/58/59 and a specificity of 100% for the tested HPV types. In cervical smear samples, HPV DNA was detected with a sensitivity of 98.14%. The overall agreement between the new HPV panel and clinical records was 97.2% (κ = 0.84). In cervical cancer cfDNA, 26/40 (65.0%) tested positive for any HPV type, with most infections due to hrHPV (24/26). HPV positive samples were found in all FIGO stages, with the highest positivity ratio in FIGO III and IV. Even the lowest stage, FIGO I, had 12/23 (52.2%) patients with a positive HPV plasma status. This proof-of-concept paper shows that the described assay produces reliable results for detecting HPV types in a multiplex mass spectrometry-based assay in cervical smear and cfDNA with high specificity and sensitivity in both cohorts. The assay shows potential for liquid biopsy-based applications in monitoring cervical cancer progression.

Human papillomaviruses and breast cancer: A systematic review and meta‑analysis.

Breast cancer (BC) is the leading malignancy worldwide. The association between human papillomavirus (HPV) and BC is debatable. The present systematic review and meta-analysis aimed to assess the prevalence of HPV DNA in malignant breast tumors. An extensive search of the PubMed and SCOPUS databases was carried out for case-control studies published between January 1, 2003 and January 7, 2023, which compared HPV DNA detection in breast tissue specimens of female patients with BC and women with absent or benign breast disorders. Once the initial title/abstract screening was completed by two independent investigators, the full texts of the included studies from that stage were reviewed by the aforementioned investigators to determine if they should be included in the present study. Data extraction was independently conducted by two investigators. A third investigator was consulted to resolve disagreements through free discussion. MedCalc was used for quantitative synthesis. The significance of association was estimated by pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated using the random-effects model. A total of 23 primary studies, including 3,243 subjects (2,027 patients and 1,216 controls), were eligible for quantitative analysis. HPV prevalence in patients with BC and controls was 21.95 and 8.96%, respectively. The prevalence of HPV differed significantly between the two groups (OR 3.83; 95% CI 2.03-7.25; P<0.01). Heterogeneity among studies was quantified using the I2 index which was 69.57% (95% CI 51.89-80.75). The risk of bias was assessed using an appropriate tool contributed by the CLARITY Group at McMaster University. Seven studies had a low risk of bias, 15 studies had a moderate risk of bias and only one study had a serious risk of bias. These results reinforce the hypothesis that HPV is involved in BC development and progression, indicating a possible role of HPV vaccination in BC prevention.

A pilot study on salivary HPV DNA detection to monitor active disease from patients with recurrent respiratory papillomatosis

PurposeRecurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-related disease affecting the upper airway and saliva could be an important non-invasive sampling source for viral screening and clinical monitoring. We investigated whether HPV DNA could be detected in saliva (cellular pellets and supernatant) from RRP patients and influence on clinical manifestation of the disease. Materials and methodsIn this pilot study, saliva samples from 14 RRP patients were obtained in preoperative condition (n = 7) and in disease-free interval (DFI; n = 7). Healthy donors (n = 14) were also included. HPV DNA was investigated by polymerase chain reaction (PCR)-based assays. ResultsFrom cellular pellets, HPV-positive saliva was only detected from preoperative collections (5/7; 71.4 %) and showed a mean cycle threshold (Ct) value of 24.33 (±1.25), whereas all patients in DFI were HPV-negative (Ct ≥ 32.16), revealing significant difference between these two clinical moments (p = 0.021). Patients in DFI and healthy donors showed similar Ct values. From saliva supernatant, detectable HPV cell-free DNA (cfDNA) occurred in 42.9 % (3/7) and 57.1 % (4/7) of preoperative collections using the commercial cfDNA kits from Norgen and Qiagen, respectively. Salivary cfDNA size distribution obtained by TapeStation analysis showed a predominant size range of 150 to 400 bp in both patients and healthy controls, corresponding to mononucleosomal and dinucleosomal fragments. ConclusionsIn conclusion, HPV DNA screening in saliva (both cellular pellets and cfDNA) may have clinical utility to monitor active disease of RRP patients.

HPV testing versus p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: results from the DAHANCA 19 study

Introduction The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. Materials and methods We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. Results HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected. Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). Conclusion In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.

A human papillomavirus whole genome plasmid repository: A resource for HPV DNA quality control reagents.

Well characterized reference reagents are useful for assay validation, proficiency/competency assessment, daily run controls, and to improve inter-laboratory comparisons. Synthetic human papillomavirus (HPV) DNA fragments and plasmid clones are available, but synthetic fragments include limited segments of the HPV genome and many HPV plasmids have interrupted coding regions or contain partial genomes. As a result, they are not compatible with all HPV DNA detection and typing assays. To address this need, we are establishing an HPV plasmid repository of HPV clones containing the whole genome of each type with no interruptions in coding regions. To date, HPV plasmid clones for 16 HPV types, (including all vaccine types and 14 types in clinical assays: HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) have been constructed using a Gibson assembly method and validated by sequencing and the Novaplex HPV typing assay. The newly constructed HPV whole genome plasmids can serve as a quality control reagent resource for HPV DNA assays and are available for public health and research laboratories.

Skin surface material for detecting human papillomavirus infection of skin warts.

Warts, caused by human papillomavirus (HPV) infection, have various clinical presentations, making them difficult to differentiate from clavus, callus, and sometimes, squamous cell carcinoma. Although skin biopsies are the gold standard, a less-invasive method of examining these lesions is desired. Ninety patients with warts and related diseases, such as clavus and callus, were recruited to explore new differentiation methods using the surface of the warts. DNA was extracted from three types of specimens in each case: surface swab, shaved hyperkeratotic scale, and post-shaved surface swab. Total DNA was successfully extracted from these three specimens and was sufficient for subsequent HPV DNA detection. We analyzed samples for the HPV type and HPV viral load using polymerase chain reaction (PCR). Fifty-five cases were PCR-positive, and HPV1a, 2a, 4, 27, 57, and 65 were detected. The amount of HPV1a DNA produced was significantly greater than that of other HPV types. Regarding the correlation between the clinical diagnosis and HPV detection, the positive agreement rate was 90.9%, the negative agreement rate was 40.0%, and the overall agreement rate was 71.1%. Ten of the 21 cases clinically diagnosed as plantar warts were PCR-negative, especially in elderly patients. This suggests that it is difficult to distinguish plantar warts from clavus and callus in clinical practice. Although the amount of HPV DNA in the removed keratinization scale was highest for all HPV types, HPV detection by swabbing before and after shaving is also useful for follow-up as well as for differential diagnosis.

Assessment of the relationships between invasive endocervical adenocarcinoma and human papillomavirus infection and distribution characteristics in China: According to the new WHO classification criteria in 2020

ObjectiveTo assess the association between endocervical adenocarcinoma (ECA) and HPV (Human papillomavirus) infection, as well as the characteristics of ECA distribution in China. MethodsA total of 756 specimens were collected from seven geographic regions across China. All cases were histologically categorized according to the 2020 WHO classification of female genital tract cancers, and 496 cases were included. We performed the SPF10-DEIA-LiPA25 assay on all specimens' whole tissue sections using PCR (WTS-PCR) to detect HPV DNA and 141 WTS-PCR HPV-positive specimens were selected for the laser capture microdissection (LCM). ResultsFour predominant prevalent histological categories of ECA in China were usual type (51.8%, 257), invasive stratified mucin-producing carcinoma (iSMILE) (11.5%, 57), mucinous NOS (not otherwise specid) (10.3%, 51), and gastric type (7.9%, 39). HPV positivity was 91.4% (235/257), 100.0% (57/57), and 90.2% (46/51) in usual type, iSMILE, and mucinous NOS by WTS-PCR detection, respectively (P < 0.001). LCM-PCR results showed a decreasing trend in HPV DNA positivity, and 21 (95.5%) patients with HPV-I were negative for HPV-DNA in glandular epithelial tissue. The most prevalent HPV genotypes in ECA were HPV16 (47.5%), 18 (40.8%), and 52 (6.5%). The average age of patients with HPVA was 44.9 years, while that of patients with HPV-I was 49.1 years, HPVA is more prevalent in younger females in China (P < 0.001). ConclusionsIn China, the predominant prevalent histological category of ECA is the usual type of adenocarcinoma, followed by iSMILE. Additionally, patients with HPVA tended to be younger than those with HPV-I.

Global and regional estimates of genital human papillomavirus prevalence among men: a systematic review and meta-analysis

The epidemiology of human papillomavirus (HPV) in women has been well documented. Less is known about the epidemiology of HPV in men. We aim to provide updated global and regional pooled overall, type-specific, and age-specific prevalence estimates of genital HPV infection in men. We conducted a systematic review and meta-analysis to assess the prevalence of genital HPV infection in the general male population. We searched Embase, Ovid MEDLINE, and the Global Index Medicus for studies published between Jan 1, 1995, and June 1, 2022. Inclusion criteria were population-based surveys in men aged 15 years or older or HPV prevalence studies with a sample size of at least 50 men with no HPV-related pathology or known risk factors for HPV infection that collected samples from anogenital sites and used PCR or hybrid capture 2 techniques for HPV DNA detection. Exclusion criteria were studies conducted among populations at increased risk of HPV infection, exclusively conducted among circumcised men, and based on urine or semen samples. We screened identified reports and extracted summary-level data from those that were eligible. Data were extracted by two researchers independently and reviewed by a third, and discrepancies were resolved by consensus. We extracted only data on mucosal α-genus HPVs. Global and regional age-specific prevalences for any HPV, high-risk (HR)-HPV, and individual HPV types were estimated using random-effects models for meta-analysis and grouped by UN Sustainable Development Goals geographical classification. We identified 5685 publications from database searches, of which 65 studies (comprising 44 769 men) were included from 35 countries. The global pooled prevalence was 31% (95% CI 27-35) for any HPV and 21% (18-24) for HR-HPV. HPV-16 was the most prevalent HPV genotype (5%, 95% CI 4-7) followed by HPV-6 (4%, 3-5). HPV prevalence was high in young adults, reaching a maximum between the ages of 25 years and 29 years, and stabilised or slightly decreased thereafter. Pooled prevalence estimates were similar for the UN Sustainable Development Goal geographical regions of Europe and Northern America, Sub-Saharan Africa, Latin America and the Caribbean, and Australia and New Zealand (Oceania). The estimates for Eastern and South-Eastern Asia were half that of the other regions. Almost one in three men worldwide are infected with at least one genital HPV type and around one in five men are infected with one or more HR-HPV types. Our findings show that HPV prevalence is high in men over the age of 15 years and support that sexually active men, regardless of age, are an important reservoir of HPV genital infection. These estimates emphasise the importance of incorporating men in comprehensive HPV prevention strategies to reduce HPV-related morbidity and mortality in men and ultimately achieve elimination of cervical cancer and other HPV-related diseases. Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020. For the Spanish and French translations of the abstract see Supplementary Materials section.

Type distribution of human papillomaviruses in ThinPrep cytology samples and HPV16/18 E6 gene variations in FFPE cervical cancer specimens in Fars province, Iran

BackgroundThere exists strong evidence that human papillomavirus (HPV) is associated with cervical cancer (CC). HPV E6 is a major oncogene whose sequence variations may be associated with the development of CC. There is not sufficient data on the distribution of HPV types in ThinPrep cytology specimens and HPV 16/18 E6 gene variations among CC patients in the southwest of Iran. This study was conducted to contribute to HPV screening and vaccination in Iran.MethodsA total of 648 women screened for cervicitis, intraepithelial neoplasia or CC were included in the study. All participants underwent ThinPrep cytology testing, single-step HPV DNA detection and allele-specific reverse hybridization assays. Moreover, a total of 96 specimens previously tested positive for single infection with HPV16 or 18 were included for variant analysis. HPV16/18 lineages and sublineages were determined by PCR assays followed by sequencing the E6 gene and the construction of neighbor-joining phylogenetic trees.ResultsOverall, HPV DNA was detected in 62.19% of all the screened subjects. The detection rates of HPV DNA among individuals with normal, ASC-US, ASC-H, LSIL, and HSIL cervical cytology were 48.9%, 93.6%, 100%, 100%, and 100%, respectively. Low-risk HPVs were detected more frequently (46.9%) than high-risk (38.9%) and possible high-risk types (11.1%). Of 403 HPV-positive subjects, 172 (42.7%) had single HPV infections while the remaining 231 (57.3%) were infected with multiple types of HPV. Our results indicated a remarkable growth of high-risk HPV66 and 68 and low-risk HPV81 which have rarely been reported in Iran and HPV90 and 87 that are reported for the first time in the country. In addition, 3 lineages (A, D, and C) and 6 sublineages (A1, A2, A4, C1, D1, and D2) of HPV16, and one lineage and 4 sublineages (A1, A3, A4, and A5) of HPV18 were identified. The studied HPV16 and 18 variants mainly belonged to the D1 and A4 sublineages, respectively.ConclusionThe present study suggests that the prevalence of HPV infection in women of all age groups with or without premalignant lesions in the southwestern Iran is high and the predominant HPV types in the southwest of Iran may differ from those detected in other parts of the country. This study also highlights the necessity of not only initiating HPV vaccination for the general population but also developing new vaccines that confer immunity against the prevalent HPV types in the area and national cervical screening programs using a combination of thinPrep cytology test and HPV detection assays in order to improve the accuracy of the screening.

HPV and Covid-19 Era: effects of nonpharmaceutical interventions on HPV transmission

ABSTRACT Human papillomavirus (HPV) is considered the commonest viral cause of sexually transmitted infections. The impact of social distance measures due to Covid-19 pandemic on HPV spread is unknown. Therefore, this study has analyzed the seven-year trend of HPV prevalence in all patients tested for HPV DNA at the Microbiology and Virology Unit at Bari Policlinico. Moreover, the HPV prevalence in 2020 has been compared with the previous year ones in order to evaluate the consequences of lockdown and social distancing measures on transmission risks. From 2013 to 2020, we retrospectively analyzed 64 anal swabs, 418 biopsies, 5925 cervical-vaginal swabs, 512 cervical swabs, 104 gland swabs, 154 oral swabs, 21 seminal fluids and 503 urethral swabs. HPV DNA detection was initially performed using nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. All statistical tests were carried out by the open-source environment R 4.0.3 (R Core Team). The data were analyzed according to yearly positivity rates, temporal trend and prevalence of HPV genotypes (HPV-6, HPV-11, HPV-16, HPV-18, high risk and low risk) by age category and sex. The number of patients increased steadily from 2016 to 2019 and then decreased in 2020. There were significant differences in prevalence between females and males for HPV-6 (6.16% in females Vs 30.80% in males), HPV-11 (0.82% Vs 7.16%) and HPV-16 (7.77% Vs 5.01%). The prevalence of HPV-6 and HPV-11 significantly increased in 2020 compared to 2013–2019 (15.72% Vs 8.52 and 3.18% Vs 1.44%). On the contrary, the overall prevalence of HPV DNA remained constant in 2020 (52.84% Vs 48.44%). Over time, the prevalence of HPV DNA (Coefficient=-0.020, p-value = 0.036) and particularly high-risk genotypes (Coefficient=-0.030, p-value = 0.005) decreased in females, while low-risk genotypes (Coefficient = 0.141, p-value= < 0.001) and the prevalence of HPV DNA increased in males (Coefficient = 0.068, p-value = 0.008). During the pandemic, the number of screened patients declined, although HPV prevalence compared to 2013–2019 remained constant or increased as in the case of low-risk genotypes. It can be assumed that the reduction of the screening coverage favored the emerging of the more symptomatic low-risk infections. In conclusion, nonpharmaceutical interventions due to Covid-19 pandemic did not reduce the risk of HPV infection but it likely caused a decrease in access to health services resulting in an increased risk of undiagnosed HPV.