Quadrivalent Human Papillomavirus Research Articles

Immunogenicity of quadrivalent human papillomavirus vaccine among Alaska Native children aged 9–14 years at 5 years after vaccination

BackgroundPersistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. MethodsDuring 2011–2014, we enrolled Alaska Native children aged 9–14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). ResultsAll participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. ConclusionsAlaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination.

INDICATION OF HPV VACCINE IN THE TREATMENT OF A CHILD WITH RECURRENT LARYNGEAL PAPILLOMATOSIS

Laryngeal papillomatosis or Recurrent Respiratory Papillomatosis (PRR) is the main cause of benign laryngeal neoplasia characterized by the proliferation of epithelial lesions with the presence of warts, called papillomas. These are often multiple and recurrent, being caused by The Human Papilloma Virus (HPV). Currently, there are no surgical or curative medical treatments for the disease. The literature indicates several options, including the quadrivalent HPV vaccine. In this sense, this study sought to report a clinical case of a child with recurrent respiratory papillomatosis, with emphasis on the quadrivalent HPV vaccine used as adjuvant therapy. In this case study, it was evidenced that immunization can be used as adjuvant therapy.

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.

Cost-effectiveness analysis of single-dose or 2-dose of bivalent, quadrivalent, or nonavalent HPV vaccine in a low/middle-income country setting.

To compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting. A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix®), 2vHPV (Cecolin®), 4vHPV (Gardasil®), 9vHPV vaccine (Gardasil9®), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted. All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings. Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention.

Human Papillomavirus vaccination coverage among the female population living in the state of Goiás, Brazil, 2014-2020: a time series study.

To analyze the temporal trend of human papillomavirus (HPV) vaccination coverage among the female population aged 10 to 14 years, living in the state of Goiás, Brazil, between 2014 and 2022. This was an ecological time series study using data from the Brazilian National Health System Information Technology Department (Departamento de Informática do Sistema Único de Saúde - DATASUS); the annual vaccination coverage rate was calculated based on the number of second doses administered; the trend of the rates was analyzed using the Prais-Winsten model. A total of 407,217 second doses of the quadrivalent HPV vaccine were administered to the female population aged 10-14 years, with annual vaccination coverage rates ranging from 12.3% (2019) to 30.0% (2015), and an annual percentage change (APC) of 0.7% (95%CI 0.9; 0.2; p-value = 0.030). In Góias state, the quadrivalent HPV vaccine coverage rate was below the national target (80%), showing a stationary trend in the time series.

Human Papillomavirus Vaccination as an Adjuvant Therapy for Recurrent Respiratory Papillomatosis: Additional Case Series.

Prevention of the recurrence of recurrent respiratory papillomatosis (RRP), a neoplasm of the respiratory tract, is a challenge. Human papillomavirus (HPV) vaccine has been expected to suppress the aggressiveness of RRP. However, there has been insufficient data to verify whether HPV vaccination can serve as an adjuvant therapy option for RRP. The aim of this study was to add our data on the efficacy of HPV vaccination for RRP to the academic discipline. Twenty-four RRP patients were treated with a combination therapy of surgery and three sessions of quadrivalent HPV vaccine. The patients' clinical courses, which were HPV infection status changes, intersurgical interval, and disease severity score (Derkay's site score), were statistically analyzed before and after combination therapy. Twelve of the 24 (52.5%) RRP patients who were HPV-DNA positive turned negative after the combination therapy. The mean of intersurgical interval was significantly extended from 6.85 ± 4.49 months to 30.5 ± 27.6 months after the therapy (P <0.01). The median of Derkay's score of the participants also significantly decreased from 7.5 (interquartile range, 5-12) to 1 (interquartile range, 0-4.25) after the therapy (P <0.01). Thus, combination therapy comprising of surgery and HPV vaccination can postpone the recurrence and lessen the severity of RRP.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9–14 years versus an established quadrivalent HPV vaccine in women aged 15–26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9–14 years versus an established quadrivalent HPV vaccine in women aged 15–26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial

Human papillomavirus prevalence and vaccine effectiveness in young women in Germany, 2017/2018: results from a nationwide study.

Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged 9-17 years. We aimed to investigate HPV DNA prevalence, genotype distribution and vaccine effectiveness (VE) in women aged 20-25 years 10 years after the introduction of HPV vaccination in Germany (2018-2019), and compared these data to an equally designed study from 2010-2012. Seventy six geographical clusters were randomly selected, followed by random selection of 61 women aged 20-25 years per cluster. Participants performed cervicovaginal self-sampling and answered questions on demographics, sexual behaviour and HPV vaccination. Samples were tested for 18 high risk and nine low risk HPV genotypes. We performed chi-square tests, Fisher's exact test, unpaired Student's t-test and proportion t-test, and calculated crude and adjusted prevalence ratios (PR) and 95% CIs. Of 7,858 contacted women a total of 1,226 agreed to participate. Of these, 94 women were positive for HPV types 16 and/or 18. HPV16 prevalence was 7.0% (95% CI 5.6-8.6) and HPV18 prevalence was 0.8% (95% CI 0.4-1.5). HPV6 and HPV11 were rare with only five (0.4%; 0.1-0.9) and one (0%; 95% CI 0.0-0.5) positive tests. Seven hundred fifty-seven women (62%) had received at least one HPV vaccine dose and 348 (28%) were vaccinated as currently recommended. Confounder-adjusted VE was 46.4% (95% CI 4.2-70.1) against HPV16/18 infection and 49.1% (95% CI 8.2-71.8) against infection with at least one HPV genotype covered by the quadrivalent HPV vaccine. Compared with the 2010-2012 study results, HPV16/18 prevalence dropped from 22.5% (95% CI 19.0-26.3) to 10.3% (95% CI 7.5-13.9; p < 0.0001) in unvaccinated participants. Vaccine-covered HPV genotypes were rare among 20-25 years old women in Germany and decreased compared to the time point shortly after the start of the HPV vaccination program. HPV prevalence of almost all vaccine-covered genotypes was strongly reduced in vaccinated participants. A decrease of HPV16 and HPV18 was even observed in unvaccinated participants, compared to 2010-2012 data, suggesting indirect protection of unvaccinated women. Low VE against HPV16/18 and HPV6/11/16/18 in our study might be attributable to study design in combination with the endpoint selection of (mainly transient) HPV DNA positivity.

Intralesional bivalent and quadrivalent human papillomavirus vaccines didn't significantly enhance the response of multiple anogenital warts when co-administered with intralesional Candida antigen immunotherapy. A randomized controlled trial.

Treatment of anogenital warts (AGWs) is challenging. Candida antigen immunotherapy has been proven to be a safe and relatively effective therapeutic modality; nevertheless, some patients may experience a partial or no response. Combining Candida antigen with other immunotherapies has been proposed to improve the cure rate. Immunotherapy with human papillomavirus (HPV) vaccines has been tried with conflicting outcomes. This study aimedto assess the efficacy and safety of intralesional Candida antigen, either alone or in combination with intralesional bivalent or quadrivalent HPV vaccines, for treating multiple AGWs. Eighty patients with multiple AGWs were included and randomly assigned to four equal groups: group A treated with intralesional Candida antigen only; group B treated with intralesional bivalent HPV vaccine (Cervarix) and Candida; group C treated with intralesional quadrivalent HPV vaccine (Gardasil) and Candida; and group D (control) treated with intralesional saline. Complete clearance of lesions was detected in 40%, 20%, and 60% of patients in Candida monotherapy, Cervarix/Candida, and Gardasil/Candida groups, respectively, whereas 40%, 60%, and 20% of patients in the three groups, respectively, showed partial response. Only 10% of the control group had a partial response. Therapeutic outcomes were significantly better in the three treatment groups compared to the control group, with no statistically significant difference between the Candida monotherapy group and the combination groups, but the response was significantly better in the Gardasil/Candida group than in the Cervarix/Candida group. No statistically significant difference was found between the studied groups regarding the development of side effects. Moreover, no recurrence was detected in any of the groups throughout the 3-month follow-up period. Based on our results,combining intralesional HPV vaccines with Candida antigen immunotherapy may haveno significant benefit for treating multiple AGWs. Candida antigen may be recommended as a relatively effective and inexpensive therapeutic modality. The combination of Gardasil and Candida was also effective but very expensive. The results of the Cervarix/Candida combination were unsatisfactory. This clinical trial was registered and approved prospectively by the ethical review board at Faculty of Medicine, Zagazig University.

Treatment response and tolerability of intralesional quadrivalent versus bivalent human papillomavirus vaccine for recalcitrant warts: A randomized controlled trial

Treatment response and tolerability of intralesional quadrivalent versus bivalent human papillomavirus vaccine for recalcitrant warts: A randomized controlled trial

A single dose of quadrivalent HPV vaccine is highly effective against HPV genotypes 16 and 18 detection in young pregnant women eight years following vaccination: an retrospective cohort study in Fiji

In 2008/9, Fiji vaccinated >30,000 girls aged 9-12 years with the quadrivalent human papillomavirus (4vHPV) vaccine coverage for at least one dose was >60% (one dose only was 14%, two dose only was 13%, three doses was 35%). We calculated vaccine effectiveness (VE) of one, two and three doses of 4vHPV against oncogenic HPV genotypes 16/18, eight years following vaccination. A retrospective cohort study was undertaken (2015-2019) in pregnant women ≤23years old, eligible to receive 4vHPV in 2008/9, with confirmed vaccination status. The study was restricted to pregnant women due to the cultural sensitivity of asking about sexual behavior in Fiji. For each participant a clinician collected a questionnaire, vaginal swab and genital warts examination, a median eight (range 6-11) years post vaccination. HPV DNA was detected by molecular methods. Adjusted VE (aVE) against the detection of vaccine HPV genotypes (16/18), the comparison group of non-vaccine genotypes (31/33/35/39/45/51/52/56/58/59/66/68), and genital warts were calculated. Covariates included in the adjusted model were: age, ethnicity and smoking, according to univariate association with any HPV detection. Among 822 participants the prevalence of HPV 16/18 in the unvaccinated, one, two and three-dose groups were 13.3% (50/376), 2.5% (4/158), 0% (0/99) and 1.6% (3/189), respectively; and for the non-vaccine high-risk genotypes, the detection rate was similar across dosage groups (33.2%-40.4%, p=0.321). The aVE against HPV 16/18 for one, two and three doses were 81% (95% CI; 48-93%), 100% (95% CI; 100-100%), and 89% (95% CI; 64-96%), respectively. Prevalence of HPV 16/18 was lower among women with longer time since vaccination. A single dose 4vHPV vaccine is highly effective against HPV genotypes 16 and 18 eight years following vaccination. Our results provide the longest duration of protection for reduced dose 4vHPV schedule in a low- or middle-income country in the Western Pacific region. This study was supported by the Bill & Melinda Gates Foundation and the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

Efficacy of HPV Vaccination Regarding Vulvar and Vaginal Recurrences in Previously Treated Women: The Need for Further Evidence.

Vulvar and vaginal cancers are relatively rare cancers, but their incidence is increasing worldwide. Overall, 78% of vaginal cancers and 25% of vulvar cancers are associated with Human papillomavirus (HPV) infection. Immunization could be an option for the management of these cases. We researched and assessed the evidence on the efficacy of HPV vaccination administered to women previously treated with surgery, radiotherapy, or chemotherapy with respect to the recurrence of vulvovaginal disease. From 2006 to November 2022, only one study evaluated the efficacy of HPV vaccination with respect to preventing vulvovaginal recurrences in treated women and showed that a quadrivalent HPV vaccine administered after the surgical treatment of vulvar high-grade squamous intraepithelial lesion (HSIL) can reduce vulvar recurrence of the disease. Therefore, the efficacy of HPV vaccination with respect to vulvovaginal recurrence is still an unexplored field. Further studies are needed to produce stronger evidence in order to appropriately support interventions to protect women's health.

Prevalence of HPV infection among Thai schoolgirls in the north-eastern provinces in 2018: implications for HPV immunization policy

ObjectiveThe aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. MethodsCross-sectional surveys were conducted among grade 10 (15–16 years old) and grade 12 (17–18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-PeeⓇ device from November 2018 to February 2019. The samples were initially tested using CobasⓇ 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by AnyplexⓇ assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. ResultsPrevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. ConclusionA substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Past pregnancy, medical history, and sociodemographics are predictive of HPV vaccination status

The quadrivalent human papilloma virus (HPV) protein sub-unit vaccine nearly abolishes cervical cancer risk by preventing persistent infection with oncogenic subtypes of HPV. Unfortunately, HPV vaccination rates remain lower than anticipated. We aimed to study this trend within our region to identify what patient-specific factors influence HPV vaccination status.

Treatment of precancerous anal lesions in HIV patients: should they be treated or monitored?

Treatment of precancerous anal lesions in HIV patients: should they be treated or monitored?

Screening and detection of multivalent human papillomavirus antibodies using a high-throughput liquid chip fluoroimmunoassay system.

Immunoassays are commonly used in disease diagnosis and vaccine evaluation but can be costly and time-consuming when confronted with multivalent targets, such as antisera containing antibodies to human papillomavirus (HPV), because of their limited ability to discriminate between multiple analytes in a single reaction well. This study describes the development of a high-throughput liquid chip system that combines immunoassay techniques and magnetic beads to allow the simultaneous screening and quantitative detection of antibodies to four types of HPV using the Luminex fluoroimmunoassay system. Groups of beads embedded with fluorescent dyes at various ratios were coated with optimized HPV capture antigens and demonstrated excellent dose-dependent response to four monoclonal antibodies used as reference standards. This assay is sensitive, accurate, repeatable, and simple to perform, enabling multiplex antibody detection with a high degree of orthogonality. The performance of the Luminex system was compared with conventional immunoassays for quantitative detection of quadrivalent HPV antibodies in antisera of mice immunized with five lots of HPV vaccines, verifying the accuracy and detection efficiency of the assay. This strategy is a promising approach to characterizing antibodies present in polyclonal antisera and has promising applications in research, clinical, and industrial settings, for example, streamlining vaccine efficacy trials and vaccine lot inspection and release procedures.

HPV vaccination: a comprehensive approach to control cervical cancer

The introduction of the Human papillomavirus (HPV) vaccination poses unique challenges due to its distinct characteristics. Unlike other vaccines, it is specifically designed to prevent cancer and is targeted towards adolescent females, making it difficult to implement within existing health intervention programs. Despite consistent clinical trial results confirming its effectiveness and safety, skepticism and concerns surrounding this vaccination are not uncommon, both among the general public and professionals. The HPV vaccination plays a crucial role in preventing cervical and other anogenital malignancies, even a single dose offering significant protection compared to not being vaccinated. This emphasizes the possibility of implementing a worldwide HPV vaccination program, as a solitary dose of the quadrivalent HPV vaccine exhibits immunogenicity and provides lasting protection against HPV 16 and 18 infections, comparable to the effectiveness of the two- and three-dose vaccine regimens.

Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

EE329 Public Health and Economic Impact of a Gender-Neutral Quadrivalent Human Papillomavirus Vaccination Program in El Salvador

To assess the public health and economic impact of adding males to the existing 9-10-year-old female-only vaccination (FOV) with two-dose schedule of quadrivalent HPV vaccine (4vHPV) from the El Salvador public health system perspective.