Human Papillomavirus DNA Research Articles

Abstract B018: Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer

Abstract Purpose: Squamous cell carcinoma of the anus (SCCA) is primarily driven by human papillomavirus (HPV) infection. Up to 30% of patients experience recurrence, necessitating improved surveillance strategies. Liquid biopsies have shown promise as a tool in oncology. This study investigates the clinical performance of circulating tumor tissue modified viral (TTMV)- HPV DNA in the post-treatment surveillance of SCCA. Patients and methods: This central IRB-approved retrospective cohort study included 117 patients diagnosed with HPV-driven SCCA from seven U.S. centers who had ≥1 TTMV-HPV DNA tests (NavDx®, Naveris, Inc., Waltham, MA) performed between March 2020 and June 2024. TTMV-HPV DNA for HPV subtypes 16, 18, 31, 33, and 35 were analyzed using droplet digital PCR. The diagnostic accuracy of TTMV-HPV DNA was evaluated by comparing test results with clinical evidence of SCCA recurrence determined through anoscopy, radiology, and/or tissue biopsy. Recurrence is defined as either a positive biopsy or subsequent salvage therapy. Results: Patients were primarily female (73%) with a median age 63 years. Median follow-up after initial treatment was 19 months. Forty-seven patients (40%) had pretreatment TTMV-HPV DNA testing, with a baseline detectability of 85.1% (40/47, 95% CI: 74.9–95.3). Of these, 24 were re-tested within 3 months post-treatment and 18 had undetectable TTMV-HPV DNA (75%). Those patients whose scores became undetectable had significantly longer recurrence-free survival than those whose scores remained detectable (log-rank test, p=0.01). One hundred and four patients (89%) underwent post-treatment testing, of which 91 provided relevant data for the analysis. Of these 91 patients, 27 (29.7%) experienced recurrence. Post-treatment testing demonstrated a per- patient sensitivity of 85.7% (24/28, 95% CI: 72.8-98.7). Of four patients with a false negative test, only one had biopsy-confirmed recurrence, whereas the remaining recurrences were not biopsied prior to starting salvage treatment. The positive predictive value of a single positive test was 97.6% (40/41; 95% CI: 92.8–100.0). One patient remains in active follow-up. Of the true positive post-treatment tests, 58% (14/24) predicted recurrence before clinical detection, with a median lead time of 59 days (range: 10–536). There were 141 negative post-treatment tests across 66 patients. This yielded a per-test specificity and negative predictive value of 99.3% (136/137, 95% CI: 97.8-100.0) and 97.2% (136/140, 95% CI: 94.9-99.9), respectively. Indeterminate TTMV-HPV DNA tests were rare (5/268,1.9%). However, clinically indeterminate findings (CIFs) were common, with 141 post-treatment CIFs identified across 52/117 patients (44.4%). TTMV-HPV DNA testing was able to correctly predict recurrence status in 94.3% of CIF cases. Conclusion: TTMV-HPV DNA testing is a sensitive and specific surveillance method for detecting early recurrence of HPV-driven SCCA. Citation Format: Shane Lloyd, Rafi Kabarriti, James Jabalee, Tyler Slater, Corbin Jacobs, Sean Inocencio, Michael Rutenberg, Chance Matthiesen, Kasha Neff, Gene-Fu F Liu, Tiffany M Juarez, Catherine DV Fitz, Stanley Liauw. Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B018.

Abstract A012: Analytical validation of a cfDNA-based fragmentomic profiling assay for the detection and quantification of 14 HPV types in cervical cancer

Abstract Purpose: Human papillomavirus (HPV) is the primary cause of cervical cancer, one of the most common cancers affecting women globally. Despite advances in prevention and screening, there remains a critical need for reliable, non-invasive assays to detect and monitor HPV-driven cervical cancers. Liquid biopsy offers a promising solution to meet this need. Here, we report the analytical validation of a plasma-based fragmentomic profiling assay designed to detect and characterize circulating tumor tissue modified viral (TTMV)-HPV DNA from 14 HPV types associated with cervical cancer. Methods: A high-complexity, laboratory-developed test was developed that employs 68 primers and 34 probes to target 14 HPV types via droplet digital PCR (ddPCR). A quantitative algorithm was applied to integrate fragment counts to generate a TTMV-HPV DNA Score, reflective of the quantity of circulating tumor-derived HPV DNA. Analytical validation was performed by determining the limit of blank (LOB), limit of quantitation (LOQ), and limit of detection (LOD) for each HPV type. To measure the limits of assay performance, engineered samples were used for reference interval studies. Synthesized target-specific DNA regions of HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, HPV66, and HPV68 were diluted to varying concentrations to perform assay validation. Results: The assay demonstrated excellent specificity, with LOBs ranging from 0 to 0.07 copies/µL across the 14 HPV types. LODs ranged from 0.20 to 1.02 copies/µL, indicating a high level of sensitivity. The assay also showed high accuracy and precision, with coefficients of variation (CV) below 20% for all HPV types across both intra- and inter-assay precision studies. Regression analysis confirmed strong linearity (R2 > 0.99) across a wide range of analyte concentrations. Conclusion: These results demonstrate that TTMV-HPV DNA assay accurately and reproducibly detects circulating HPV DNA for 14 HPV types commonly associated with cervical cancer, offering a valuable tool for both diagnosis and ongoing surveillance in clinical settings. Future studies will present the clinical validation in order to establish the prognostic utility of the assay in predicting the likelihood of HPV-driven cervical cancer in patients. Citation Format: Sunil Kumar, Joshua Hutcheson, David Conway, Michael Horan, Syandan Chakraborty, Chloe Wiseman, Alicia Gunning, Evgeny Skyrypkin, Cassin Williams, Catherine Del Vecchio Fitz, Piyush B Gupta. Analytical validation of a cfDNA-based fragmentomic profiling assay for the detection and quantification of 14 HPV types in cervical cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A012.

The radiological features of HPV-positive vs HPV-negative OPSCC at a South African hospital

Background: Studies have found that, at presentation, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has a less advanced primary tumour, more advanced lymph node spread and commonly has cystic metastatic lymph nodes in comparison to HPV-negative OPSCC.Objectives: To compare the radiological features of HPV-positive and HPV-negative OPSCC in South African patients.Method: A retrospective cross-sectional study was conducted at a large South African hospital. Eligibility required a histologically proven OPSCC between 2007 and 2023; a p16 antigen test and, if positive, a confirmatory HPV DNA PCR test and a baseline pre-treatment contrast enhanced neck CT scan. All eligible HPV-positive OPSCC patients and a random sample of eligible HPV-negative OPSCC patients were enrolled.Results: Twenty-one HPV-positive and 55 HPV-negative OPSCC patients were recruited. There was no statistically significant difference in the tumour epicentre location, local advancement (≥ T3 in 67% and 71%, respectively, p = 0.54), mean primary tumour size (41 mm vs. 39 mm, p = 0.73), lymph node spread (bilateral or more in 67% vs. 82%, p = 0.22) or morphologically cystic lymph nodes (10% and 4%, p = 0.61).Conclusion: There was no statistically significant difference in the CT imaging appearances of HPV-positive and HPV-negative OPSCC in the studied sample of South African patients.Contribution: This study documents the radiological features of OPSCC in a small South African sample population, where HPV-positive and HPV-negative OPSCC could not be distinguished on CT criteria and did not display the classic features described in the literature.

CRISPR-Cas12a-regulated DNA adsorption on MoS2 quantum dots: Enhanced enzyme mimics for sensitive colorimetric detection of human monkeypox virus and human papillomavirus DNA

Diseases caused by viruses, such as monkeypox virus (MPXV) and human papillomavirus (HPV), pose serious threats to human health and safety. Although numerous strategies have been constructed for detecting MPXV and HPV DNA, most methods require either laborious procedures or complicated instruments involving skilled professionals. In this research, a CRISPR-Cas12a-mediated colorimetric detection platform for MPXV and HPV sensing was constructed for the first time by applying probe DNA to reprogram the catalytic properties of molybdenum disulfide quantum dots (MoS2 QDs). In the presence of MPXV or HPV targets, the CRISPR-Cas12a trans-cleavage activity is effectively motivated to decompose the probe DNA, leading to the suppression of enzymatic activity DNA enhancer adsorbed on MoS2 QDs, resulting in greatly decreased catalytic behaviors. The MoS2 QDs-DNA nanohybrids displayed prominent specificity and sensitivity, with detection limits at subpicomolar levels, as well as excellent stability and accuracy for determining MPXV and HPV DNA in human sera biosamples. Furthermore, the proposed colorimetric biosensing approach can be ensembled with a smartphone platform, allowing visible analysis of DNA targets. Taken together, this colorimetric strategy offers a novel diagnosis method for MPXV and HPV DNA detection, particularly favorable for highly endemic developing countries with restricted medical and instrumental support.

Circulating tumor HPV DNA as a specific biomarker for cervical cancer.

The aim of this study was to determine whether circulating tumor human papillomavirus (HPV) DNA is a potential specific biomarker for cervical cancer (CC). This retrospective matched study included 87 patients with cervical intraepithelial neoplasia (CIN), 29 CC patients (FIGO IA1-IVA) and 29 HPV-negative controls at Yuhuangding Hospital of Qingdao University (from July 2022 to September 2023). The digital droplet PCR (ddPCR) was used to detect and quantify ctHPV DNA in the plasma of patients with HPV16, 18, 33, 52, or 58-associated CC. The ctHPV DNA was exclusively detectable in HPV-positive samples, with no detection in patients across various CIN stages (n = 87) or HPV-negative controls (n = 29). Additionally, ctHPV DNA was identified in nine out of 10 late-stage patients (90%) and six out of 19 early-stage patients (31.6%). The ctHPV DNA serves as a specific biomarker for the diagnosis CC. Additionally, this discovery addresses the knowledge gap in ctHPV DNA research in the early stages of CC and promotes clinical diagnosis and treatment strategies.

Impact of single-dose HPV vaccination on HPV 16 and 18 prevalence in South African adolescent girls with and without HIV

Abstract Background The World Health Organization has endorsed single-dose human papillomavirus (HPV) vaccination, but data on the impact on HPV prevalence in high HIV burden settings are limited. Methods A single-dose bivalent HPV vaccine was delivered to adolescent girls in grade 10 in a schools-based campaign in 1 district in South Africa. Impact on HPV 16 and 18 prevalence was evaluated using repeat cross-sectional surveys. A clinic-based survey in girls aged 17-18 years established HPV 16 and 18 prevalence in a prevaccine population (n = 506, including 157 living with HIV) in 2019 and was repeated in the same age group and sites in a single-dose eligible population in 2021 (n = 892, including 117 with HIV). HPV DNA was detected on self-collected vaginal swabs using the Seegene Anyplex II HPV 28. Population impact was estimated overall and by HIV status using prevalence ratios adjusted for differences in sexual behavior between surveys. Results Single-dose vaccination campaign coverage was 72% (4807 of 6673) of eligible girls attending high school (n = 66) in the district. HPV 16 and 18 prevalence was 35% lower in the postvaccine survey overall (adjusted prevalence ratio = 0.65, 95% confidence interval [CI] = 0.51 to 0.83; P < .001) and 37% lower in those living with HIV (adjusted prevalence ratio = 0.63, 95% CI = 0.41 to 0.95; P = .026). No protective effect was seen for nonvaccine oncogenic HPV types 33, 35, 39, 51, 52, 56, 58, 59, or 68 overall (adjusted prevalence ratio = 1.14, 95% CI = 1.03 to 1.26; P = .011) or in those living with HIV (adjusted prevalence ratio = 1.00, 95% CI = 0.83 to 1.21. P = 0.99). Conclusion These data provide reassuring evidence of single-dose impact on population-level HPV 16 and 18 prevalence in a South African population, irrespective of HIV status.

Molecular Pathogenesis of Human Papillomavirus: Insights into Viral Oncoproteins and Host Integration

Human Papillomavirus (HPV) is a major cause of death from cervical cancer and other anogenital cancers throughout the world. Pathogenicity of HPV is governed by intricate interplay of HPV and host cells mediated primarily by its oncoproteins E6 and E7. These oncoproteins disrupt critical pathways, including those involving tumor suppressors p53 and retinoblastoma (Rb) to induce unregulated cell proliferation and evasion of apoptosis. These mechanisms have been studied in order to develop the different diagnostic tools, such as HPV DNA testing and genotyping, and there are emerging techniques based on E6/E7 mRNA detection and high throughput sequencing. In addition, therapeutic strategies have advanced with the vaccines showing ability to prevent high risk HPV infection and ongoing research to developing targeted therapies to disrupt viral oncoprotein function. New diagnostic and therapeutic approaches to HPV research encompassing an expanding clinical landscape hold promise to reduce incidence of HPV associated malignancies and improve patient outcomes. This review summarizes the molecular pathogenesis of HPV with respect to host cells and discusses its implications for diagnostics and therapeutics, including the need for further development in this area.

A case of squamous cell carcinoma of the lung misdiagnosed as tuberculosis. Is HPV infected by oral sex the causative agent?

BackgroundThe integration of high-risk human papilloma virus (HPV) DNA into the human genome has been implicated in cervical carcinogenesis and head and neck squamous cell cancer. However, its role in lung squamous cell carcinoma is not well understood. In addition, tuberculosis (TB) and lung cancer(LC) share similar clinical symptoms and imaging features, increasing the risk of misdiagnosis.Case PresentationThe patient presented with a 16-month history of hemoptysis, chest pain, and occasional fatigue, without fever, chills, or history of mechanical damage or autoimmune diseases. Examination revealed normal vital signs and laboratory parameters, except for a positive interferon-gamma release assay indicating tuberculosis infection. Bronchoscopic examinations identified congestion and edema of the tracheal wall, along with a tiny lesion in the right wall of the trachea. She had been misdiagnosed with tuberculosis. However, the diagnosis of squamous cell carcinoma was eventually confirmed by endoscopic biopsy. The patient’s macrogenomic second-generation sequencing (mNGS) of the bronchoscopic biopsy specimen was positive for HPV-16.The patient’s sex partner tested positive for HPV-16 in penile scrapings, indicating HPV transmission through oral sex.ConclusionsThis case highlights the potential for HPV infection acquired through oral sex to lead to lung squamous cell carcinoma. It emphasizes the importance of considering HPV-associated malignancies in patients with respiratory symptoms who engage in oral sexual behaviors.

Exploring the Association between Human Papillomavirus (HPV) and Breast Carcinoma: A review

Anal, cervical, and oropharyngeal malignancies are all known to be caused by the human papillomavirus (HPV). However, its exact function in Breast Cancer (BC) is still up for debate. Findings from a systematic literature search shed light on the possible link between HPV and BC. There could be a connection amongst HPV infection and the development of BC, as several works have shown HPV DNA in breast carcinoma tissues. There has been some conflicting evidence on the nature of the link between HPV and BC; some research has found the virus, while others have not. Different studies have shown different patterns of HPV genotypes in BC tissue; some have identified high-risk genotypes like HPV-16 and HPV-18, while others have shown a broad range of genotypes without any discernible pattern. To explain the significance of HPV in BC cases, better-designed research with bigger sample numbers and rigorous methodology are required.

Comparison of Urine and Cervical Samples for Genotyping Via HPV DNA Test

<i>Background</i>: Human papillomavirus (HPV) is a key factor in cervical cancer development. This study aimed to compare the efficacy of urine and cervical samples for HPV genotyping, evaluating their diagnostic performance in detecting high-risk HPV genotypes. <i>Methods</i>: This comparative cross-sectional study conducted over one year at the Department of Gynaecological Oncology, BSMMU, Dhaka, the study enrolled 74 women aged 30-60 years with positive visual inspection with acetic acid (VIA) results or abnormal Pap test findings. Urine samples (20 ml) and cervical samples were collected from each participant. The samples were analyzed using multiplex real-time PCR to amplify high-risk HPV types (16, 18, and others). DNA was extracted using the Qiagen viral DNA extraction kit. Sensitivity and specificity of HPV detection in urine samples were compared to cervical sampling, the gold standard. Data were analyzed with SPSS 22.0, and agreement was assessed using the Kappa index. <i>Result</i>: Cervical samples detected HPV in 17.56% of participants, while urine samples identified HPV in 5.40%. The agreement between urine and cervical samples was moderate, with a kappa value of 0.743. Among 74 cases, 5 cases were detected as HPV 16 and HR (co-injection) in both cervical and urine sample, 2 cases as HPV 16 in both cervical and urine samples, 2 cases as only HR type in both cervical and urine sample. The kendall’s correlation of agreement was 0.361 and a significance of 0.002. <i>Conclusion</i>: Cervical samples are more reliable for HPV detection compared to urine samples, though urine testing shows high sensitivity.

Evaluation of Automatic Signal Detection of In Situ Hybridization for Detecting HPV DNA in Cervical Tissue Derived from Patients with Cervical Intraepithelial Neoplasia

Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80–90%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = −7961.82 CI95 [−17,230.00; −199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.

A review of urinary HPV testing for cervical cancer management and HPV vaccine surveillance: rationale, strategies, and limitations.

Human papillomavirus (HPV) infections are the leading cause of cervical cancer, the fourth most common cancer among women worldwide. Despite concerted efforts to combat this preventable disease through HPV vaccination and cancer screening have helped reduce morbidity and mortality levels, the burden persists in both developing and developed countries due to insufficient vaccination and screening coverage. Urinary HPV testing has emerged as a noninvasive detection method, offering significant advantages in cervical cancer management and vaccine surveillance. Notably, it boasts high acceptance rates, ease of self-collection, user-friendly implementation, and relatively low cost. Various urinary HPV detection methods have been explored, predominantly relying on nucleic acid amplification and signal amplification, targeting a variety of biomarkers in urine, such as HPV DNA, RNA, and oncoproteins. Existing literature underscores urine as a promising specimen for HPV testing, demonstrating comparable detection performance to cervical and vaginal samples in several studies. However, the lack of standardized and authoritative protocols in sample collection, storage, preparation, DNA extraction, and amplification necessitates further evaluation for the comprehensive utilization of urinary HPV testing in clinical and epidemiological settings. This study aims to review pertinent publications and offer insights into the rationale, common strategies, and limitations of urinary HPV testing, with the ultimate goal of maximizing its utility in practice.

HPV Vaccination Status in HIV-Negative MSM and Its Association with High-Risk HPV Detection Using HPV Serology and Anorectal Swabs

Background/Objective: The aim of this study was to determine the prevalence of high-risk (HR) human papillomavirus (HPV) types by HPV vaccination status and the feasibility of using HPV L1 serology to identify HIV-negative men who have sex with men (MSM) who may be at risk for anal cancer. Methods: This cross-sectional study recruited HIV-negative MSM from a US metropolitan area. The prevalence of HR, quadrivalent, and nonavalent anorectal HPV DNA and HPV L1 serum antibodies was estimated. McNemar’s chi-square and kappa statistics were used to determine significant differences in HPV detection between anorectal DNA swabs and HPV L1 serology. Results: Eighty-two men had adequate anorectal swabs and serology samples for analysis. Men who self-reported receipt of the HPV vaccine (35.6%) had detectable L1 HPV antibodies (93.1%) and a lower prevalence of active anal HPV infections (20.7%) compared to those who reported none. Conclusions: If confirmed in larger prospective studies, a combination of HPV vaccination status or HPV L1 serology and anorectal swabs for HR HPV types could identify HIV-negative MSM who do not need to undergo follow-up anal testing.

Electrochemical detection of human papillomavirus DNA based on an ultrasensitive electrochemical sensing platform using N-graphene paper

Human papillomavirus (HPV) is the primary cause of cervical cancer, a major global health concern affecting women worldwide. Early detection of high-risk HPV genotypes is crucial for timely intervention and reducing disease burden. However, current detection methods often lack sensitivity, speed, or cost-effectiveness, especially in resource-limited settings. This work addresses this critical need by developing an ultrasensitive electrochemical biosensing platform based on nitrogen-doped graphene paper electrodes for quantifying high-risk HPV16 DNA sequences. The N-graphene nanohybrid, fabricated via simple solvothermal treatment of biomass-derived graphene oxide, demonstrated significantly enhanced electrical and electrocatalytic properties compared to undoped graphene. DNA detection was achieved through characteristic oxidation signals of guanine bases, which displayed a wide linear dynamic range (0.5–100 μg/mL), low detection limit (75 pg/mL), and excellent reproducibility (relative standard deviation <3.5 %). Detailed spectroscopic and electrochemical analyses revealed the key roles of pyridinic nitrogen defects in improving interfacial charge transfer kinetics and mitigating biofouling issues. This synergistic combination of high electrical conductivity and versatile surface functionality paves the way for equipment-free, point-of-care genosensor devices tailored for quantitative biomarker screening in resource-constrained environments.

HPV is an essential driver in recurrence of cervical cancer

IntroductionHigh-risk human papillomavirus (HPV) has been detected in distant metastases from cervical cancer (CC) patients, suggesting a role of HPV. Material and methodsHere, we included 26 patients with recurrence of CC (2019-2023). With next generation sequencing (NGS) and immunohistochemical staining, primary and recurrent tissues were analyzed for HPV DNA and HPV RNA, p16INK4a expression, and somatic TP53 and RB1 mutations. ResultsAll primary and corresponding recurrent tissues were HPV DNA and HPV RNA positive. Within the same tissue, we found complete DNA/RNA agreement in 25/26 (96.2%) primary and 25/25 (100%) recurrent tissues, and partial agreement in the remaining sample. There was complete agreement between primary and recurrent tissue in 23/26 (88.5%) and 23/25 (92.0%) patients on DNA and RNA, respectively, whereas the remaining showed partial agreement with two genotypes detected in primary and only one of these in recurrent tissue. Except for one sample, all samples from high-risk HPV-positive patients were p16INK4a positive. The low-risk HPV11-positive patient was p16INK4a negative and had a pathogenic TP53 mutation, while the remaining samples were TP53/RB1 mutation negative. ConclusionIn high-risk HPV-positive CC patients, HPV seems to play a role in recurrent disease. Our findings support ongoing research on targeting HPV oncogenes in CC, also in metastatic disease.

Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.

Human papillomavirus (HPV) infections are the cause of warts, lesions and cancer, with different types of HPV causing different symptoms. HPV infections are the primary cause of cervical cancer. There are over 220 different types of HPV, and only nine of these can currently be vaccinated. There is a need to treat these viral infections without just treating the symptoms of the infection, as is currently the main method. There is a wide range of small molecules that have been used to inhibit various stages of the HPV infectious cycle. This review examined 132 small molecules from 121 studies that specifically target aspects of HPV infections. HPV DNA encodes for six early genes (E1 to E7, skipping E3) and two late genes (L1 and L2). According to the results, these targets for small molecule inhibitors fall into three categories: those targeting E1 and E2, targeting E6 and E7 and, finally, targeting L1 and L2. Inhibitors of E6 and E7 are the most widely studied targets, with the majority of HPV inhibition in this area. While compounds targeting both E1/E2 and E6/E7 have made it to clinical trials, there has been no significant advancement on the topic.

The Sansure® Human Papillomavirus DNA Diagnostic Kit offers excellent reproducibility performance for the detection of high-risk HPV.

Cervical cancer screening is a cornerstone of cervical cancer elimination. Detection of high-risk human papillomavirus (hrHPV) is recommended as the first step in screening provided that the assay used has been adequately validated. The Sansure® Human Papillomavirus DNA Diagnostic Kit is a new assay designed to detect HPV16, HPV18 and 13 other HPV in aggregate. The study aimed to evaluate the intra- and interlaboratory reproducibility of the assay according to international guidelines. Five hundred and fifty cervical residual cell samples from women attending cervical cancer screening were selected from the biobank of the HPV National Reference Centre in Belgium and used in this study. After DNA extraction, HPV was tested using the Sansure® Human Papillomavirus DNA Diagnostic Kit. The lower 95% confidence limit around the general reproducibility of this assay should be greater than or equal to 87%, with κ ≥ 0.50. Five hundred and thirty-three samples had valid results. The Sansure® Human Papillomavirus DNA Diagnostic Kit demonstrated an excellent intra-laboratory reproducibility of 93.8% (95% confidence interval [CI]: 91.4-95.7, κ = 0.85). The interlaboratory reproducibility was 93.4 (95% CI: 91.0-95.4, κ = 0.84). Intra and interlaboratory reproducibility were also excellent at the genotype level. Excluding HPV53 single infection samples from the analyses also resulted in excellent agreement. These data show that the Sansure® Human Papillomavirus DNA Diagnostic Kit is highly reproducible.

Hotspots of Anal Cancer Screening in a High-risk Population: A Clinical Study on Free Provision, Best Method, Self-sampling, and Independent Risk Factors.

As of 2024, anal cancer (AC) has been steadily increasing worldwide but, due to insufficient evidence, anal cancer screening (ACS) has yet to be standardized. Furthermore, most high-risk people in the world have no help paying for it. Therefore, our primary endpoint was to assess the best screening method for these subjects through a provision that was free of charge (all costs were covered by the Italian public health service). Awareness-raising campaign, determination of risk factors, education on anal self-examination, and sampling (ASS) were secondary objectives. Screening was on a voluntary basis. Engaging in receptive anal intercourse and having a history of cervical dysplasia were the main inclusion criteria. Level 1 ACS tools included digital ano-rectal examination, anoscopy, anal Pap, and anal human papillomavirus (HPV) DNA test (both through self- and proctologist- sampling); high-resolution anoscopy (HRA) with (HRAB) or without biopsy comprised level 2 screening. High-risk people were enrolled until the available funds were exhausted. Fifty high-risk people (40 men who had sex with men -MSM-, 9 women, and 1 heterosexual man) were enrolled. AC was found in one HIV-seropositive MSM, high-grade squamous intraepithelial lesion in 10 (20%) MSM, low-grade squamous intraepithelial lesion LSIL in 13 cases (12 MSM and 1 woman). The combination of HRAB and Pap smear screening achieved the highest values for sensitivity, specificity, and accuracy. ASS HPV DNA test provided excellent results comparable to clinician retrieval. Overweight and college education were identified as independent factors for the risk of and prevention of AC, respectively. A free ACS not only appears justified but also recommended to people screened for AC. Excess weight represents a further risk for this population.

Progress and Challenges in Canada's Path Toward the Elimination of Cervical Cancer.

Cervical cancer is almost entirely preventable and treatable when detected early, making its elimination within reach for Canada and the world. However, cervical cancer is now the fastest-increasing cancer (+3.7% per year since 2015) in Canada as of 2023, marking the first significant increase in cervical cancer incidence since 1984. The human papillomavirus (HPV) vaccine and cervical screening are key preventive measures, with targets set by the WHO and the Canadian Partnership Against Cancer (CPAC) to eliminate cervical cancer in Canada by 2030 and 2040, respectively. These targets include increasing HPV vaccination rates, implementing primary HPV screening, and improving follow-up for abnormal HPV+ results. However, Canada's progress has been impeded by significant challenges. As of the most recent data, HPV vaccine coverage rates in Canada range from 47% to 81%, with an estimated national HPV vaccination completion rate of 64% in Canada, far below the target of 90% by 2025 set by the CPAC. With the exception of British Columbia and Prince Edward Island, the adoption of HPV DNA testing as the primary screening method has been slow across the Canadian provinces and territories despite its superior sensitivity compared with traditional cytology. This article reviews the current state of HPV vaccination and screening in Canada, emphasizing the need for coordinated efforts, transparency, and resource sharing to overcome barriers. Key recommendations include the dissemination of accessible educational materials, partnerships, and collaboration, including nationwide task forces and roundtables, and the implementation of standardized guidelines for HPV screening. Achieving cervical cancer elimination requires a united approach involving federal, provincial, and territorial health authorities, researchers, clinicians, NGOs, community groups, and patients' voices working together to ensure consistent, effective, timely, and meaningful cervical cancer prevention strategies are used across the country.