Prophylactic Human Papillomavirus Vaccines Research Articles

Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Molecular dynamics simulation and purification of chimeric L1/L2 protein from human papillomavirus type 52 expressed in Escherichia coli BL21 (DE3)

ABSTRACT The available prophylactic vaccines for human papillomavirus (HPV) in the market are only effective against specific types of HPV, rendering them ineffective for other types of HPV infections. The objective of this research is to investigate the stability of the recombinant protein constructed, namely chimeric L1/L2 protein from HPV type 52, with improved cross-neutralization ability. The 3D model, predicted using Alphafold, Robetta, I-Tasser, and refined with Galaxy Refinement, is validated using Ramachandran plot analysis. The stability is verified through molecular dynamics simulations, considering parameters such as RMSD, RMSF, Rg, and SASA, where stable conditions are observed. The chimeric L1/L2 protein from HPV type 52 is purified using affinity chromatography, and the His-tag is cleaved using SUMO protease to obtain pure chimeric protein with the size of ~ 55 kDa. Western blot analysis confirms binding to anti-L1 HPV type 52 polyclonal antibody. The obtained vaccine candidate can be utilized as an effective prophylactic vaccine against HPV.

The Non-inferiority of Human Papillomavirus Vaccine Immunogenicity Among Women Over 26 Years: A Systematic Review.

Demonstrate the immunogenicity of the human papillomavirus (HPV) vaccine for the older age group (above 26 years) to prevent HPV infection with high-risk types and argue for extending vaccination recommendations for the older age group. Two authors searched PubMed, Embase, and the Cochrane Library from inception to December 2023 to collect information on clinical trials of HPV vaccine immunogenicity. The database search strategy used a combination of subject terms and free terms. Two authors first identified studies by reading the title, abstract, and full texts and, subsequently, based on the inclusion criteria. Studies eligible to be included are the clinical trials using one of the following types of HPV vaccines: 2vHPV, 4vHPV, and 9vHPV, and measuring the immunogenicity by the geometric mean concentration or titer (GMC/T) and seroconversion rate (SCR) among healthy women aged 9 to 55 years who had never received a prophylactic HPV vaccine, known serostatus for HPV, non-immunocompetence, or non-pregnant. This review included nine articles, seven RCTs, and two open-labeled studies. In summary, we have demonstrated that the immunogenicity of the HPV vaccines is non-inferior in the older age group. Even though the GMT declines with age, the SCR is similar in all age groups regardless of the serostatus. The immunogenicity of the bivalent vaccine is superior to that of the quadrivalent vaccine for the older age group. Additionally, the vaccine is more efficient in women under the age of 26, but older women will benefit from it.

Current status and future directions for the development of human papillomavirus vaccines.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

Gardasil® as adjunctive therapy for respiratory papillomatosis at Red Cross Children’s Hospital, Cape Town

Background: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is an incurable condition caused by human papilloma virus (HPV) types 6 and 11, often requiring repeated surgeries and in severe cases, tracheostomy. This imposes a significant socioeconomic burden on patients and families. Gardasil®, a proven prophylactic HPV vaccine, is emerging as a potential adjuvant therapy. We studied its response on JoRRP patients at our center.Methods: We conducted a retrospective review at Red Cross War Memorial Children’s Hospital from January 2015 to June 2022 on histologically confirmed JoRRP cases. Age at diagnosis, baseline and post-dosing Derkay-Coltrera (DC) scores (disease severity measure), inter-surgical intervals and tracheostomy, were collected.Results: Twenty-five of 30 confirmed cases were included. Average age at diagnosis was 60 months (about 5 years old), with HPV Type 6 in 40% and Type 11 in 48% of patients. All patients received at least one Gardasil® dose, 84% received a second dose and 64% a third dose. Total population DC score decreased from an average of 17 (range: 4-34) pre-first dose to 8 (range: 0-16) after three doses, indicating a 50% reduction. Surgical intervals modestly increased. More significant improvements were seen in patients with aggressive forms of the disease.Conclusion: This is the first study in Southern Africa highlighting Gardasil® as adjuvant therapy. Despite our limited sample size, new cases observed a linear reduction in DC scores and tracheostomy rates.Contribution: This suggests that Gardasil® as adjuvant therapy has the potential to reduce disease severity and extend surgical intervals.

Assessing the reduction of viral infectivity in HPV16/18-positive women after one, two, and three doses of Gardasil-9 (RIFT): Study protocol.

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.

Cervical cancer prevention by vaccination: review.

Routine use of human papillomavirus (HPV) vaccines is recommended in adolescents under 15 years of age worldwide. Still, effective programs remain suboptimal for several factors, making the WHO strategy to eradicate cervical cancer public health with an uncertain future. To review the literature on the effectiveness, long-term protection, and safety of HPV vaccination programs and vaccination as adjuvant management. This review aims to describe the current state of vaccination programs and demonstrate the long-term protection and safety of vaccines implemented worldwide targeting adolescent girls, with the most recent published evidence of the three prophylactic HPV vaccines - bivalent (bHPV), quadrivalent (qHPV), and nonavalent (nHPV)-. We mainly focus on publications evaluating efficacy, dosing schemes, and HPV vaccination, as well as studies contributing to the mounting evidence for the real-life effectiveness of prophylactic HPV vaccines from several countries. Human Papillomavirus vaccination programs have made remarkable strides in preventing HPV-related diseases; countries with robust vaccination efforts have witnessed substantial reductions in HPV-related diseases with a decline in high-grade cervical abnormalities and genital warts (54%-83%). However, global coverage remains uneven, with disparities between high-income (HICs) and low-income countries (LMICs). The long-term efficacy of the available human papillomavirus (HPV) goes up to 9.4 years and continues to be immunogenic and well tolerated with an excellent safety profile. As these are crucial topics in HPV vaccination, it is essential to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.

Dynamic borrowing of historical controls adjusting for covariates in vaccine efficacy clinical trials.

Traditional vaccine efficacy trials usually use fixed designs and often require large sample sizes. Recruiting a large number of subjects can make the trial expensive, long, and difficult to conduct. A possible approach to reduce the sample size and speed up the development is to use historical controls. In this paper, we extend the robust mixture prior (RMP) approach (a well established approach for Bayesian dynamic borrowing of historical controls) to adjust for covariates. The adjustment is done using classical methods from causal inference: inverse probability of treatment weighting, G-computation and double-robust estimation. We evaluate these covariate-adjusted RMP approaches using a comprehensive simulation study and demonstrate their use by performing a retrospective analysis of a prophylactic human papillomavirus vaccine efficacy trial. Adjusting for covariates reduces the drift between current and historical controls, with a beneficial effect on bias, control of type I error and power.

HPV Vaccine Optimization Concerning Cervical Cancer

Cervical cancer, associated with human papillomavirus (HPV), is currently the fourth most prevalent cancer among women in the world. Though nowadays there are HPV vaccines available on the market, more strategies need to be taken to improve them and develop more therapeutic vaccines. Recent research has mostly concentrated on the state of HPV vaccinations, including their mechanisms, clinical efficacy, and room for improvement. However, there is a significant research deficit in the field of therapeutic HPV vaccination development. This paper analyzes the mechanisms of both prophylactic and therapeutic HPV vaccines, analyzes the clinical efficacy of five major vaccines in China, and discusses strategies for optimizing HPV vaccines through adjuvants and targeted antigen design. This thorough analysis offers insightful perspectives on the efficacy and safety of the HPV vaccine and makes recommendations for further study and immunization campaigns. However, the problems about the impact of vaccination programs and HPV-related diseases in men haven’t been solved yet. Therefore, future studies should target developing therapeutic HPV vaccines, improving HPV vaccines in the next generation, increasing the awareness of the public, and increasing accessibility of vaccines to release the burden of cervical cancer globally.

Vaccine and Non-Vaccine HPV Types Presence in Adolescents with Vertically Acquired HIV Five Years Post Gardasil Quadrivalent Vaccination: The ZIMGARD Cohort.

Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study. This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5-6 years before enrolment. We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12-16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types. The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of 'opportunistic non-vaccine HPV types' or 'ecological niche occupiers' in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH.

A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide.

Cervical cancer has been considered as one of the most common cancers in women (15-44 years) globally, but the advent of the human papilloma virus (HPV) vaccine has raised the anticipation that eradication of cervical carcinoma might be achieved in the near future as several prophylactic cervical carcinoma vaccines have already been currently licensed in various countries. Countries should devise strategies, practices and policies to attain and sustain higher levels of HPV immunization coverage as still 68% countries have introduced HPV vaccine in their national immunization programs even after 17 years following the licensure of the first prophylactic HPV vaccine. A comprehensive literature analysis was conducted using various databases and search engines, to include the most relevant research articles and data available and critically discussed the operational gaps that need to be answered to achieve adequate coverage of HPV vaccination. The present review highlights the existing HPV vaccination strategies, unmet needs and challenges needed to be addressed for proper implementation framework as well as the collaborations required to achieve decent vaccination coverage. Well-coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.

Humani papilomavirusi i karcinom grlića materice iz perspektive inicijative Svetske zdravstvene organizacije za eliminaciju karcinoma grlića materice

Human papillomaviruses (HPV) are the most common sexually transmitted pathogens worldwide, leading to infections with a wide range of clinical manifestations: from benign conditions to different types of cancer in women and men as well. Cervical cancer is highly correlated with persistent high-risk-HPV (HR-HPV) infection, which is the key factor in emergence of 99.99% of cervical cancer cases. The most effective way to prevent HPV-related cancers is vaccination. There are three available prophylactic HPV vaccines: bivalent, quadrivalent and nonavalent. The nonavalent vaccine is gradually replacing other HPV vaccines in most countries and can be given from year 9, but it is commonly routinely implemented at the age of 11 to 12. The World Health Organization has recognised cervical cancer as a global threat and has announced the so-called 90-70-90 strategy to reduce and even eliminate cervical cancer. This strategy implies that 90% of girls should be vaccinated by the age of 15, 70% of women should be screened for cervical cancer, and 90% of women diagnosed with cervical disease should receive adequate treatment. Although different treatment options are available: surgery, radiation therapy, chemotherapy, and advanced target therapy using monoclonal antibodies, great efforts are needed to achieve the goals set by the World Health Organization to eliminate cervical cancer.

A single-injection vaccine providing protection against two HPV types.

Prophylactic human papillomavirus (HPV) vaccines against cervical cancer were successfully developed; however, challenges such as high cost and low compliance still remain to be overcome. In addition, because many HPV types can cause cervical cancer, antigens of multiple HPV types are needed to achieve broad protection. In this study, a bivalent single-injection HPV vaccine was designed in which virus-like particles (VLPs) of HPV 16 L1 and HPV 18 L1 were used as antigens. A recently developed drug carrier that uses tannic acid/polyethylene glycol films as the erodible layer was employed to accomplish multiple pulsatile releases of the antigens. Monovalent single-injection vaccines for HPV 16 and HPV 18 were first designed. A bivalent single-injection vaccine was then obtained by simply mixing the two monovalent vaccines. The bivalent vaccine provided protection against both HPV types. More importantly, it elicited both humoral and cellular immune responses as potent as those elicited by the corresponding multiple dose vaccine because of their similar release profile of antigens. Cross-reactivity was observed between HPV 16 and 18 in terms of cellular immune responses, while no cross-reactivity was found in terms of humoral immune responses. Note that other multivalent single-injection vaccines could be designed in the same way. These vaccines are expected to help prevent cervical cancer because of their broad protection, enhanced compliance and lowered vaccination cost.

Treatment of Cervical Precancers is the Major Remaining Challenge in Cervical Screening Research.

Deepening understanding of cervical cancer pathogenesis has yielded one-dose prophylactic human papillomavirus (HPV) vaccines and accurate HPV-based cervical screening tests. Knowing the heterogeneous carcinogenic potential of the individual high-risk HPV types permits prioritization of vaccination and screening strategies. However, "correct" (i.e., safe and effective) treatment of women found to have precancer is still undefined, forcing reliance on one or more rounds of untargeted destructive/excisional treatment. Both over-treatment and under-treatment are common results. Until safe and effective anti-HPV therapies are invented, defining optimal destructive/excisional treatment of precancer remains a fundamental and under-researched challenge, especially in resource-constrained settings. See related article by King et al., p. 681.

Advances on two serological assays for human papillomavirus provide insights on the reactivity of antibodies against a cross-neutralization epitope of the minor capsid protein L2.

A second generation of prophylactic human papillomavirus (HPV) vaccines based on the minor capsid protein L2 has entered clinical trials as promising alternative to meet the gaps left out by the current vaccines concerning type-restricted protection, high costs and low penetrance in immunization programs of lowand middle-income countries. Most of the serological assays available to assess anti-HPV humoral responses are, however, not well suited for measuring vaccine-induced anti-L2 antibody responses. In this work, we have advanced our automated, purely add-on High-Throughput Pseudovirion-Based Neutralization Assay (HT-PBNA) in an L2-oriented approach for measuring antibody-mediated neutralization of HPV types 6/16/18/31/33/52/58. With the optimized settings, we observed 24- to 120-fold higher sensitivity for detection of neutralizing Ab to the L2 protein of HPV6, HPV16, HPV18, and HPV31, compared to the standard HT-PBNA. Alternatively, we have also developed a highly sensitive, cell-free, colorimetric L2-peptide capture ELISA for which the results were strongly concordant with those of the advanced neutralization assay, named HT-fc-PBNA. These two high-throughput scalable assays represent attractive approaches to determine antibody-based correlates of protection for the HPV L2 vaccines that are to come.

Immuno-Oncology In Cancer Cervix Treatments: Literature Review

It is an unhappy truth that regardless of being almost fully preventable through human papillomavirus(HPV) vaccination and screening, cervical cancers remains the fourth most common cancers to have an effect on women. High risk HPV infection (hrHPV) is the number one etiological element for cervical cancer. Upto 70% of instances are via HPV types 16 and 18, with many different hrHPV related to the rest of cases. Modern-day trendy- of- care treatments consist of radiotherapy, chemotherapy, and/ or surgical resection. still, they have got good sized side effects and limited efficacy against advanced disease. there are few treatment choices for recurrent or metastatic cases. Immunotherapy gives new stopgap, as demonstrated with the aid of the current blessing of PD1 blocking antibody for recurrent or metastatic disease. This might be augmented by way of mixture with antigen-specific immunotherapy tactics, comparable as vaccines or adoptive cellular transfer, to enhance the host cell immune response targeting HPV-positive cancer cells. As cervical cancers progresses, it is able to foster an immunosuppressive medium and counteract host anticancer immunity. therefore, procedures to reverse suppressive susceptible surroundings and bolster effector T cellular functioning are probable to enhance the success of comparable cervical cancers immunotherapy. The success of non-specific immunostimulants like imiquimod against genital warts additionally propose the possibility of exercising those immunotherapeutic strategies in cervical cancer prevention to deal with precursor lesions(cervical intraepithelial neoplasia) and affected person hrHPV infections against which the licensed prophylactic HPV vaccines haven't any efficacy. We assessed the progress and demanding situations inside the development of immunotherapeutic processes for the prevention and treatment of cervical cancer.

New Paradigms in the Treatment of Cervical Cancer.

Despite effective screening strategies and the development and implementation of prophylactic high-risk human papillomavirus vaccination, cervical cancer remains a significant public health burden. This burden is most pronounced in under-resourced countries without fully developed screening and vaccination programs, although the disease remains present worldwide, including in industrialized countries. To that end, the World Health Organization (WHO) has an active focus on the elimination of cervical cancer, with objective metrics to be achieved by countries by the year 2030. Although increased vaccination and screening will be needed to approach potential eradication of cervical cancer, as recognized by the WHO initiative, treatment will need to continue to not only be effective in the near term, but to improve outcomes as well. Accordingly, assessments to improve primary treatment options, including surgery for women with early-stage disease, modification of chemoradiation for those with locally advanced cervical cancer, and systemic therapy for those with recurrent or metastatic presentations, are ongoing. Accordingly, we highlight important areas of both recent and ongoing focus as they relate to improving cervical cancer outcomes.

Trend of HPV Molecular Epidemiology in the Post-Vaccine Era: A 10-Year Study.

Cervical cancer, a major health concern among women worldwide, is closely linked to human papillomavirus (HPV) infection. This study explores the evolving landscape of HPV molecular epidemiology in Taiwan over a decade (2010-2020), where prophylactic HPV vaccination has been implemented since 2007. Analyzing data from 40,561 vaginal swab samples, with 42.0% testing positive for HPV, we reveal shifting trends in HPV genotype distribution and infection patterns. The 12 high-risk genotypes, in order of decreasing percentage, were HPV 52, 58, 16, 18, 51, 56, 39, 59, 33, 31, 45, and 35. The predominant genotypes were HPV 52, 58, and 16, accounting for over 70% of cases annually. The proportions of high-risk and non-high-risk HPV infections varied across age groups. High-risk infections predominated in sexually active individuals aged 30-50 and were mixed-type infections. The composition of high-risk HPV genotypes was generally stable over time; however, HPV31, 33, 39, and 51 significantly decreased over the decade. Of the strains, HPV31 and 33 are shielded by the nonavalent HPV vaccine. However, no reduction was noted for the other seven genotypes. This study offers valuable insights into the post-vaccine HPV epidemiology. Future investigations should delve into HPV vaccines' effects and their implications for cervical cancer prevention strategies. These findings underscore the need for continued surveillance and research to guide effective public health interventions targeting HPV-associated diseases.

HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China.

To explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues in central and eastern China and to provide theoretical basis for cervical cancer screening and prophylactic HPV vaccine development in China. DNA was extracted from paraffin-embedded tissues of CSCC samples and exfoliated cervical cells of cervical cancer screening populations. 23 HPV genotypes were detected by combining polymerase chain reaction (PCR) and reverse dot hybridized gene chip detection technology in 2,306 CSCC tissues and 10,245 cervical cancer screening populations. The genotype distribution of HPV infection was analyzed. The overall infection rate of HPVs in 2,306 CSCC patients was 92.71%. The frequency of single-type HPV infection and multiple-type HPV infection were 86.48% and 13.51%, respectively. The most common HPV genotypes detected in Chinese CSCC tissues were HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, and HPV-59. The overall positivity rate of these eight high-risk HPV (HR-HPV) genotypes in HPV-positive CSCC was as high as 96.91%. Of which the positivity rate of seven HR-HPV genotypes related to nine-valent HPV vaccines in HPV-positive CSCC was 95.09%. Meanwhile, the overall infection rates of HR-HPV and low-risk HPV (LR-HPV) in female aged 35-64 years who underwent cervical cancer screening were 13.16% and 1.32%, respectively. The high-frequency HR-HPV genotypes in cervical cancer screening women were HPV-52, HPV-58, HPV-16, HPV-53, HPV-68, HPV-39, HPV-51, and HPV-56, with positivity rates of 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, and 0.74%, respectively. Among women screened for cervical cancer in China, detecting the 8 high-frequency HR-HPV genotypes can reduce technical difficulty and reagent costs, while also improving the efficiency and effectiveness of cervical cancer screening. HPV genotyping assists gynecologists in assessing the risk of HR-HPV-positive cervical intraepithelial neoplasia and guiding them in implementing appropriate interventions. Furthermore, HPV genotyping is helpful for doctors to follow up HR-HPV-positive women and to evaluate the protective effect of HPV vaccine.

Recent Developments in Human Papillomavirus (HPV) Vaccinology.

Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic HPV is HPV-16, which dominates the types causing cancer. There is also sufficient evidence that HPV types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 cause cervical cancer. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralising antibodies, forms the basis of all commercial HPV vaccines. There are six licensed prophylactic HPV vaccines: three bivalent, two quadrivalent and one nonavalent vaccine. The bivalent vaccines protect from HPV types 16 and 18, which are associated with more than 70% of cervical cancers. Prophylactic vaccination targets children before sexual debut, but there are now catch-up campaigns, which have also been shown to be beneficial in reducing HPV infection and disease. HPV vaccination of adults after treatment for cervical lesions or recurrent respiratory papillomatosis has impacted recurrence. Gender-neutral vaccination will improve herd immunity and prevent infection in men and women. HPV vaccines are immunogenic in people living with HIV, but more research is needed on the long-term impact of vaccination and to determine whether further boosters are required.