High-risk Human Papillomavirus Types Research Articles

Prevalence of HPV Genotypes among Greek Women in Association with Their Potential to Cause Precancerous Lesions.

The escalating global rates of precancerous lesions associated with human papillomavirus (HPV) types not targeted by current vaccines underscore the need to explore the prevalence of HPV types within the Greek female population and their involvement in precancerous lesion development. In the current study, we enrolled a cohort of 253 women aged 18 to 65 years, residing in Greece, who underwent routine screening in three tertiary care referral hospitals. Each participant completed a demographic questionnaire. An HPV DNA test was administered using the VisionArray® HPV kit (ZytoVision GmbH) to qualitatively detect and genotype 41 clinically relevant HPV genotypes. Of all 253 women examined, 114 (45.1%) tested positive for HPV DNA. The primary type detected was HPV51 (high-risk), present in 21 women (8.3% of the total), followed by HPV54 (low-risk) in 17 women (6.7%); HPV16 (high-risk) ranked third, identified in 14 women (5.5%). Among the HPV-positive women, 65 were positive for high-risk HPV types (57% of HPV-positive women) and were referred for colposcopy and cervical biopsy. These procedures identified 24 women with cervical intraepithelial neoplasia 1 (CIN1) lesions and 2 with cervical intraepithelial neoplasia 2 (CIN2) lesions. The most prevalent HPV type among women with CIN1 lesions was HPV16, found in nine (37.5%) women, while HPV51 ranked second, identified in six (25%) women. Both women with CIN2 lesions tested positive for HPV16, whereas one of them was also tested positive for HPV45. Our study is the first to report the prevalence of HPV51 among HPV-positive women in the Greek female population. This highlights the need for further research to fully understand the potential of HPV types not covered by current vaccines, such as HPV51, to cause high-grade lesions or cervical cancer.

Transition of DNA-HPV over time in HPV-infected women: a 7-year cohort study

BACKGROUND Approximately 99% of cervical cancer cases worldwide are associated with one of the high-risk human papillomavirus (HPV) types. This study aimed to determine the transition rate of DNA-HPV over time in women aged 18–69 years with HPV infection in Can Tho City, Vietnam, from 2013 to 2020. METHODS The 2-phase cohort study was conducted on 213 women between 2013 and 2020. Phase 1 involved a retrospective cohort study (2013–2018), and phase 2 included a prospective cohort study (2018–2020). HPV testing was performed using real-time polymerase chain reaction on cervical fluid. McNemar’s test was employed to compare differences in HPV transition between 2013 and 2020. RESULTS From 2013 to 2018, the transition, clearance, and non-transition rates were 17.1%, 65.8%, and 66.2%, respectively, revealing a significant difference in the number of HPV cases during this period (p = 0.007). From 2018 to 2020, the transition, clearance, and non-transition rates were 9.8%, 44.9%, and 82.2%, respectively. Overall, the DNA-HPV changes from 2013 to 2020 indicated rates of 14.3% for transition, 68.5% for clearance, and 67.1% for non-transition. A significant difference in HPV cases was found between 2013 and 2020 (p = 0.001). CONCLUSIONS The longer duration resulted in a more significant difference in the DNA-HPV transition among HPV-infected women.

Aptima HPV Genotypes in Abnormal Cervical Samples in Different Age Groups - Implication on Vaccination Strategies.

Persistent infection with high-risk human papillomavirus (hr-HPV) types is associated with high-grade cervical abnormalities. The aim of the study was to find most hr-HPV types causing persistent infection in abnormal cytological samples using Aptima HPV testing and discuss the compatibility of the Gardasil 9 vaccine in targeting most types. The study was conducted in a cytology laboratory in a tertiary hospital. This is a retrospective observational study. Cytology and HPV Aptima test reports were obtained for abnormal cervical samples for a 6-year period. Pearson Chi-square test. Reports of 2834 abnormal cervical samples were analyzed. Aptima testing was positive in 21% of samples, including 92% of squamous cell carcinoma (SCC), 76.4% of the high-grade squamous intraepithelial lesion (HSIL), 52% of low-grade squamous intraepithelial lesion (LSIL), 40% of adenocarcinoma (ADC), and 21% of atypical squamous cells that cannot exclude HSIL (ASC-H). The Aptima other hr-HPV group was most common (60%), HPV16 was 26%, HPV18/45 was 9.6%, and double HPV infection was 4.3%. HPV16 was the most common infection in HSIL+ cases. HPV infection was most common in age groups (30-39) and (40-49), and a shift to age groups (50-59) and ≥60 was seen in HSIL+ cases. This study is the first of its kind in correlating age with hr-HPV and cytology findings in the Middle East and adds to previous knowledge related to the prevalence and Aptima testing of HPV. The outcome could be used as a baseline for the Gardasil 9 vaccine and for the assessment of its effectiveness after three or five years from initiation.

Cationic Liposomes Carrying HPV16 E6-siRNA Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells.

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.

Do HPV 16 positive/ASC-H cervical cancer screening results predict CIN 2+ better than other high-risk HPV subtypes?

To determine whether patients with atypical squamous cells, cannot exclude high grade squamous intraepithelial neoplasia (ASC-H) cytology have a correlation between high-risk human papillomavirus (HPV) type and CIN 2+1 lesion in final pathology. The study was conducted retrospectively, using data from three tertiary gynecologic oncology centers located in various regions of Turkey. Data from 5,271 patients who had colposcopy between January 2003 and January 2021 were analyzed. A total of 163 patients who had ASC-H cervical cytology test results, based on the Bethesda 2014 classification were eligible, and of these 83 (50.9%) who tested positive for HPV were included in the study. There was no correlation between the occurrence of CIN 2+ lesions and age (p=0.053). If there was any HPV 16 positivity (only HPV 16, HPV 16 and 18, HPV 16 and others) the presence of CIN 2+ lesions in the final pathology increased significantly. In HPV 16 positive ASC-H patients, the probability of CIN 2+ lesions in the final pathology were 72.5% while this rate was 48.1% in HPV 16 negative group (p=0.033). The guidelines do not provide a comprehensive definition of the role of the HPV test in managing ASC-H. Positive high-risk HPV types, especially HPV 16, together with an ASC-H smear result should bring to mind the possibility of high-grade dysplasia.

Retrospective Cross-Sectional Epidemiological Study of Human Papillomavirus-Associated Precancers and Anogenital Warts in Patients Attending Specialized Clinics in Russian Federation

Background. In Russia, there are no country level registries on HPV-associated pre-cancers (cervical intraepithelial neoplasia, CIN; vulvar intraepithelial neoplasia, VIN; vaginal intraepithelial neoplasia, VaIN; anal intraepithelial neoplasia, AIN; penile intraepithelial neoplasia PIN) and anogenital warts (AWs) and no national-level cervical cancer screening program. Aims — the aim of this study was to assess the proportion of patients with CIN, VIN, VaIN, AIN, PIN and AWs diagnosis in the clinical settings in Russia. Methods. This study was a non-interventional retrospective multi-center chart-review study in 28 investigational sites representing 21 Federal subjects of 6 Federal Districts of Russia. Medical charts of adult men and women visited gynecology, sexual health, dermatovenerology or urology services between 1 Jan 2000 — 31 Dec 2019 were reviewed. Data were abstracted, using a standardized approach, on patient demographic characteristics, presence or absence of pre-cancers and AWs diagnoses, method of diagnosing pre-cancer and HPV infection, and grade of neoplasia. Results. A total of 11 520 patients (1732 male and 9788 female) were included in the analysis. The overall proportion of patients with HPV-associated precancers and AWs was 10.8%. By service type, cases of HPV-associated conditions were revealed most often in dermatological departments (14.5%) and gynecological hospitals (13.8%). CIN detection rate in Russian clinical settings increased over the 20-years from 3.2 to 11.1% and was higher in gynecological in-patient departments compared to out-patient departments (12.5 and 5.2% respectively). The number of non-cervical precancers (VIN, VaIN, AIN, PIN) cases were very low (the detection rate was less than 1%). The frequency of HPV type 16 and 18 detection increased from 0.6 to 4.8%, and from 0.2 to 1.9%, respectively, for the 20-years period. Conclusions. Our study suggested high level of HPV-related pre-cancer and AW disease burden as well as presence of high-risk HPV types. Preventive strategy through effective national HPV immunization program would be beneficial to reduce HPV-related disease burden in Russia.

Impact of human papillomavirus types on uterine cervical neoplasia.

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV-associated cervical lesions is HPV genotype-dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high-risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high-risk HPVs, HPV18 has some peculiar characteristics different from those of other high-risk HPV types; the detection rate in precancerous lesions is much lower than those of other high-risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell-like cells. In this context, this review outlines the natural history of HPV-infected cervical lesions and the characteristics of each HPV genotype.

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Risk of cervical high-grade squamous intraepithelial neoplasia in cytologic negative and persistently high-risk human papillomavirus positive patients according to genotypes: a retrospective single center analysis

In January 2020, a different cervical cancer screening program started in Germany. Women above the age of 35 are recommended to have a combined HPV and cytology swab every three years. Showing persistent high-risk human papillomavirus (hrHPV), cytologic negative cervical samples at baseline and after 12 months, patients are referred to colposcopy. Entailing considerable additional workload due to the required colposcopies, we analyzed the risk of high-grade cervical intraepithelial neoplasia (CIN 3) in cytologic negative and persistent hrHPV women according to their hrHPV genotypes.Methods In this single center retrospective study, patients with persistent hrHPV, cytology negative cervical samples from our certified Colposcopy Unit in 2020 and 2021 were analyzed. Patient demographics, hrHPV types, biopsy rates and histological reports were collected.Results During the study, 69 patients were enrolled. Most frequent hrHPV genotypes were: hrHPV other 72.5%; HPV 16, 20.3% and HPV 18, 7.2%. Colposcopy showed no or minor changes in 92.7% and major changes in 7.2%. CIN 3 was found in 7 patients (10.1%). Prevalence of CIN 3 by hrHPV genotypes was 27.3% for HPV16, 20.0% for HPV18 and 7.1% for HPVO. A statistically significant dependency between hrHPV and cervical intraepithelial neoplasia was demonstrated (p = 0.048).Conclusion Within this single center study of persistent hrHPV, cytologic negative samples, patients with HPV 16 were more likely to have high-grade disease compared to other hrHPV subtypes. Larger prospective randomized trials are needed to substantiate our results and obtain adjusted cervical cancer screening time intervals according to the hrHPV genotypes.

Intra‐ and interlaboratory reproducibility evaluation toward international validation status of the AmpFire assay

AbstractTo meet the screening goal of WHO's 90‐70‐90 strategy aimed at eliminating cervical cancer (CC) by 2030, clinical validation of human papillomavirus (HPV) assays is essential to provide accurate and valid results through fulfilling three criteria of the international validation guidelines (IVGs). Previously, the clinical accuracy of the AmpFire® HPV Screening 16/18/HR assay (AmpFire assay) was reported but reproducibility data are lacking. Here, we aim to evaluate the intra‐ and inter‐laboratory reproducibility of the AmpFire assay. The reproducibility of the isothermal AmpFire assay was assessed using 556 cervical cell samples collected from women attending CC screening and biobanked in a Belgian HPV national reference center. This assay detects HPV16, HPV18, and 12 other high‐risk HPV (hrHPV) types (31/33/35/39/45/51/52/56/58/59/66/68) in aggregate. Lower 95% confidence interval bound around the assay's reproducibility should exceed 87%, with κ ≥ 0.50. Additionally, a literature review of the assay's clinical performance was performed. The AmpFire assay showed an excellent intralaboratory (96.4%, 95% CI:94.5–97.8%, κ = 0.920) and interlaboratory (95.3%, 95% CI:93.2–96.9%, κ = 0.897) reproducibility. One study demonstrated noninferior sensitivity of a prototype AmpFire assay targeting 15 hrHPV types (including HPV53) to detect CIN2+. However, clinical specificity became similar to the comparator after removing HPV53 from analyses. The low‐cost and easy‐to‐use AmpFire assay presents excellent reproducibility and—after removing HPV53 from the targeted types—fulfills also clinical accuracy requirements. Inclusion of HPV53, which is not recognized as carcinogenic, comprises clinical specificity of screening assays.

A phase 2 study to evaluate efficacy and safety of PRGN-2009, a novel gorilla adenovirus-based immunotherapy, in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer.

TPS5623 Background: The association between cervical cancer and human papillomavirus (HPV) is well understood, with nearly all cervical cancer known to be caused by high risk HPV infection. HPV16 and HPV18 are the most common high-risk HPV types and are responsible for about 70% of cervical cancer cases. Recurrent or metastatic cervical cancer is currently treated with pembrolizumab alone or in combination with chemotherapy, however t there remains a significant need for treatments for patients that recur or do not respond at all to pembrolizumab treatment. PRGN-2009 is a gorilla adenovirus-based immunotherapy targeting cancers caused by HPV16 or HPV18. PRGN-2009 includes a novel HPV antigen design to induce HPV16/18-specific T cell immune responses against cancer cells. The rationale for combining the PRGN-2009 with immune checkpoint inhibitor is based on preclinical and clinical data demonstrating that combination of cancer vaccines and immune checkpoint inhibitors can trigger intensified immunogenicity leading to increased antitumor efficacy compared to either treatment alone. PRGN-2009 has been characterized in both in vitroand in vivostudies to support the scientific rationale and the safety of PRGN-2009 has been demonstrated in evaluated in initial Phase 1/2 studies in patients with HPV+ malignancies. Methods: This is a randomized, Phase 2 study to evaluate efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with recurrent or metastatic cervical cancer. Key inclusion criteria include recurrent or metastatic cervical cancer (histologically or cytologically confirmed) resistant to pembrolizumab. Subjects will be randomized 1:1 to Cohort 1: Combination of PRGN-2009, 5 x 1011 PU (Day 0, Day 21 and Day 42, then q6w), plus pembrolizumab, 400mg q6w, or to Cohort 2: pembrolizumab alone (400 mg q6w). Subjects randomized to Cohort 2 (pembrolizumab monotherapy) and who have confirmed disease progression (per RECIST 1.1) after at least one cycle of pembrolizumab and have had no Grade ≥ 3 adverse events related to treatment will be offered the option to crossover to Cohort 1 (PRGN-2009 plus pembrolizumab). All subjects will be evaluated for safety and efficacy of PRGN-2009 in combination with pembrolizumab, and for biological correlative assays. The primary endpoint is objective response rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab monotherapy, and will be tested using Fleming’s two-stage design and the stopping boundaries for futility and efficacy applied. The study is currently recruiting patients with recurrent or metastatic cervical cancer (NCT06157151). Clinical trial information: NCT06157151 .

Internal validation of Automated Visual Evaluation (AVE) on smartphone images for cervical cancer screening in a prospective study in Zambia.

Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance. Prospective study. Eight public health facilities in Zambia. A total of 8204 women aged 25-55. Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Area under the receiver operating curve (AUC); sensitivity; specificity. As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91). These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).

Development and validation of an assay to quantify plasma cell-free human papillomavirus DNA for 13 high-risk types that cause 98% of HPV-positive cancers.

6065 Background: Plasma cell-free HPV DNA (cfHPV) may be a valuable tool for identification of patients with local-regionally advanced HPV-positive cancers at risk for recurrence after chemoradiation. Technical validation is required for use as an integral biomarker in a prospective clinical trial. Methods: Cell-Free 13 (i.e., CF13) is a digital-droplet PCR assay for quantification of 13 high-risk HPV types and control ERV3 in plasma that considered both variant sequences into primer/probe design and a distance matrix in phylogenetic analysis in multiplex combinations. Oligonucleotides/plasmids encoding type-specific E6/E7 regions were used as positive controls. Limit of blank, detection, quantification (LoB, LoD, LoQ), linear range, inter- and intra-assay coefficients of variation (CoV), and type-specific cross-reactivity were determined as were sensitivity and specificity for an HPV-positive diagnosis in a cohort of 278 oropharyngeal/unknown primary/oral cavity cancers tested for HPV by E6/E7 mRNA qRT-PCR or p16 IHC and HPV in situ hybridization. Results: Under identical assay conditions, the LoB, LoD and linear range were <1, 5 and 5 to 200,000 virus copies without HPV type-specific cross-reactivity. Multiplexing had no effect on LoD or linearity. LoQ was 16 copies/ml plasma for all 13 HPV types. For 80 and 10,000 copies per ml, inter-assay CoV ranged from ~15-28% and ~3.2-4.6% and intra-assay CoV ranged from ~16-38% and 0.2-3.3%, respectively. cfDNA purification method (manual v automated; extraction efficiency 142% and 91% for 16 and 10,000 HPV16 copies/ml), input plasma volume (1, 2, or 4 ml), total background cfDNA (<1800ng) or genomic DNA (<700ng) did not affect quantification. For a diagnosis of HPV-positive cancer, sensitivity and specificity were 91.1% (214/235) and 97.7% (42/43), respectively. cfHPV was associated with gender, race, T stage, N stage, and primary treatment modality. When compared to below the median (≤230 copies/ml), cfHPV above the median was associated with worse progression-free survival (HR=2.26, 95% CI 1.23-4.17, p=0.009) in univariate analysis. However, this was no longer significant after adjustment for age, T stage, and M stage (HRadj=1.78, 95% CI 0.95-3.35, p=0.07). Conclusions: CF13 has high sensitivity, accuracy, precision, linearity, HPV type-specificity, and robustness, offering a rigorously validated assay applicable to ~98% of patients with HPV-positive cancer. CF13 had excellent clinical sensitivity and specificity for a diagnosis of HPV-positive OPC.

Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.

Structure-Based Discovery of Potential HPV E6 and EBNA1 Inhibitors: Implications for Cervical Cancer Treatment

Cervical cancer is the fourth most diagnosed cancer and the fourth leading cause of cancer death in women globally. Its onset and progression have been attributed to high-risk human papillomavirus (HPV) types, especially 16 and 18, while the Epstein–Barr virus (EBV) is believed to also significantly contribute to cervical cancer growth. The E6 protein associated with high-risk HPV strains, such as HPV16 and HPV18, is known for its role in promoting cervical cancer and other anogenital cancers. E6 proteins contribute to the malignant transformation of infected cells by targeting and degrading tumor suppressor proteins, especially p53. On the other hand, EBV nuclear antigen 1 (EBNA1) plays a crucial role in the maintenance and replication of the EBV genome in infected cells. EBNA1 is believed to increase HPV E6 and E7 levels, as well as c-MYC, and BIRC5 cellular genes in the HeLa cell line, implying that HPV/EBV co-infection accelerates cervical cancer onset and growth. Thus, the E6 and EBNA1 antigens of HPV and EBV, respectively, are attractive targets for cervical cancer immunotherapy. This study, therefore, virtually screened for potential drug candidates with good binding affinity to all three oncoviral proteins, HPV16 E6, HPV18 E6, and EBNA1. The compounds were further subjected to ADMET profiling, biological activity predictions, molecular dynamics (MD) simulations, and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations. A total of six compounds comprising ZINC000013380012, ZINC000070454124, ZINC000014588133, ZINC000085568136, ZINC000095909247, and ZINC000085597263 demonstrated very strong affinity (≤−60 kJ/mol) to the three oncoviral proteins (EBNA1, HPV16 E6, and HPV18 E6) after being subjected to docking, MD, and MM/PBSA. These compounds demonstrated relatively stronger binding than the controls used, inhibitors of EBNA1 (VK-1727) and HPV E6 (baicalein and gossypetin). Biological activity predictions also corroborated their antineoplastic, p53-enhancing, Pin1 inhibitory, and JAK2 inhibitory activities. Further experimental testing is required to validate the ability of the shortlisted compounds to silence the insidious effects of HPV E6 and EBNA1 proteins in cervical cancers.

Comparative evaluation of Anyplex II HPV28 and Allplex HPV28 molecular assays for human papillomavirus detection and genotyping in anogenital cancer screening.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

High frequency of alpha7-HPV in Colombian Caribbean coast women: cervical cancer screening analysis

SUMMARYBackgroundCervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening.MethodsA cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and − 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value < 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software.ResultsWe included 450 women, mean age 40 (SD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document}11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18–31.63). Menopause was protective (OR=0.31; 95% CI 0.11–0.89).ConclusionsOur study reveals a notable prevalence of multiple (2–4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.

Surface material analysis for human papillomavirus detection in nail Bowen's disease caused by HPV type 58.

Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its similarity to nail malignant melanoma, particularly with respect to the clinical manifestation of black nail streaks. While skin biopsy is usually employed for diagnosis, it is an invasive procedure. We report the case of a 52-year-old healthy Japanese male with a pigmented streak on the nail of the fourth finger of his right hand, which had extended from the central to the lateral nail fold within 4 months. Dermoscopic examination revealed a dark-brown pigmented band with splinter microhemorrhage. Clinically, nail Bowen's disease was suspected. The lesion was excised in strips under local anesthesia. Histopathological examination revealed hyperkeratosis, parakeratosis, papillomatosis, and dyskeratotic cells with atypical nuclei irregularly arranged. Immunohistochemistry using anti-HPV L1 antibody detected HPV-positive cells in the upper epidermis and stratum corneum of the nail matrix. Mucosal high-risk HPV type 58 DNA was detected from brush cytology of the keratotic surface prior to surgery, which was confirmed in formalin-fixed, paraffin-embedded excised samples using polymerase chain reaction (PCR) and subsequent direct DNA sequencing. Our case highlights HPV type 58 as a potential causative agent of nail Bowen's disease and shows that brush cytology of the surface material prior to excision may be a useful and less invasive way for mucosal high-risk HPV detection. PCR analysis of the nail surface could serve as a supplementary diagnostic tool for nail Bowen's disease.

The future of cervical cancer prevention: advances in research and technology

This article provides an informative overview of the current situation and future trends in cervical cancer prevention. Cervical cancer remains a significant public health concern worldwide and is characterized by notable variations in both incidence and mortality rates between developed and developing countries. This underscores the importance of understanding the pathophysiology of cervical cancer, stressing the involvement of high-risk HPV types. The presence of supplementary risk factors facilitates the transition from infection to cancer. This review examines current preventive methods, including the success of HPV vaccines such as Gardasil and Cervarix, and the effectiveness of screening techniques, from cytology to HPV DNA testing. It noted the limitations faced by primary and secondary preventive measures, particularly in low-resource settings, which include access to vaccines and effective screening procedures. Emerging technologies in cervical cancer prevention, such as liquid-based cytology, molecular testing, and AI, promise to improve early detection and diagnosis accuracy and efficiency. The potential of precision medicine to customize treatment based on individual risk factors was discussed. It explores the innovation in genetic editing techniques, such as CRISPR/Cas9, in targeting HPV oncoproteins, the advent of immunotherapy, the role of tumor-infiltrating lymphocytes, and the prospects of biomarkers in improving early detection. Research and technological advancements are leading to transformative changes in cervical cancer prevention. These developments suggest a path toward improved screening, diagnosis, and treatment that could significantly reduce the global burden of the disease. However, realizing the full potential of these advances requires inclusive research and international collaboration to overcome access disparities, particularly in resource-limited settings.

Let’s open our eyes to the importance of vaginal microbiota. Correlation between dysbiosis and HPV infection: A review

Infections with the human papillomavirus (HPV) are one of the most common sexually transmitted diseases and are the main cause of precancerous changes and cervical cancer development. However, mere infection does not guarantee the development of disease or carcinogenesis. For this to occur, high-risk types of HPV must integrate into the host cell genome, transitioning into a persistent form of infection. Following the discovery of risk factors for HPV infection and factors predisposing infection to a persistent form, the number of studies investigating the correlation between vaginal dysbiosis and infection has significantly increased. Numerous studies document a significant association between the state of vaginal bacterial flora and HPV infection, leading to the development of plentiful studies on infection pathogenesis, risk factors, prevention, and treatment methods using bacteria. In this paper, based on recently published studies and current state of science knowledge, we will outline the topic of vaginal microbiome, emphasize the importance of bacteria inhabiting the vagina for human health, and identify the problem of changes in vaginal microflora. We would like to contribute to the dissemination of knowledge about the vaginal microbiome and general knowledge about taking care of its health. We will also summarize available treatment methods based on bacterial environment and discuss those methods for which research is currently underway or should be initiated.