Opportunities and challenges for human papillomavirus vaccination in China.

Current estimates of the HPV infection rate in China vary by geographic region (9.6-23.6%), with two age peaks in prevalence in women ≤20-25 years of age and 50-60 years of age. HPV-16, 52 and 58 are the most commonly-detected HPV genotypes in the Chinese population. In China, five HPV vaccines are licensed and several others are undergoing clinical trials. Multiple RCTs have shown the efficacy and safety of the bvHPV (Cervarix), Escherichia coli-produced bvHPV (Cecolin), Pichia pastoris-produced bvHPV (Walrinvax), qvHPV (Gardasil) and 9vHPV (Gardasil-9) vaccines in Chinese populations, including two studies showing long-term efficacy (≥8 years) for the bvHPV and qvHPV vaccines. Real-world data from China are scarce. Although modeling studies in China show HPV vaccination is cost-effective, uptake and population coverage are relatively low. Various policies have been implemented to raise awareness and increase vaccine coverage, with the long-term aim of eliminating cervical cancer in China.

Safety and immunogenicity of Innovax bivalent human papillomavirus vaccine in girls 9-14 years of age: Interim analysis from a phase 3 clinical trial.

BACKGROUND: World Health Organization human papillomavirus (HPV) vaccination recommendations include a single- or two-dose schedule in individuals 9-20 years old and advice for generating data on single-dose efficacy or immunobridging. The ongoing Phase 3 trial of Innovax's bivalent (types 16 and 18) HPV vaccine (Cecolin®) assesses in low- and middle-income countries alternative dosing schedules and generates data following one dose in girls 9-14 years old. Interim data for the 6-month dosing groups are presented. METHODS: In Bangladesh and Ghana, 1,025 girls were randomized to receive either two doses of Cecolin at 6-, 12-, or 24-month intervals; one dose of Gardasil® followed by one dose of Cecolin at month 24; or two doses of Gardasil 6 months apart (referent). Serology was measured by enzyme-linked immunosorbent assay (ELISA) and, in a subset, by neutralization assays. Primary objectives include immunological non-inferiority of the Cecolin schedules to referent one month after the second dose. Safety endpoints include reactogenicity and unsolicited adverse events for 7 and 30 days post-vaccination, respectively, as well as serious adverse events throughout the study. RESULTS: Interim analyses included data from the two groups on a 0, 6-month schedule with 205 participants per group. One month after Dose 2, 100% of participants were seropositive by ELISA and had seroconverted for both antigens. Non-inferiority of Cecolin to Gardasil was demonstrated. Six months following one dose, over 96% of participants were seropositive by ELISA for both HPV antigens, with a trend for higher geometric mean concentration following Cecolin administration. Reactogenicity and safety were comparable between both vaccines. CONCLUSIONS: Cecolin in a 0, 6-month schedule elicits robust immunogenicity. Non-inferiority to Gardasil was demonstrated one month after a 0, 6-month schedule. Immunogenicity following one dose was comparable to Gardasil up to six months. Both vaccines were safe and well tolerated (ClinicalTrials.gov No. 04508309).

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

HPV vaccines induce trained immunity and modulate pro-inflammatory cytokine expression in response to secondary Toll-like receptor stimulations.

Cervical cancer is caused mostly by human papillomavirus (HPV), and several HPV vaccines have been developed to prevent its onset. Vaccines include antigens as well as adjuvants, with adjuvants playing an important role in activating the innate immune responses necessary for inducing adaptive immunological responses. Recent research has shown the presence of trained immunity inside the innate immune system. However, trained immunity conferred by HPV vaccinations is not well understood. In this work, we explored the innate immune responses and trained immunity caused by two HPV vaccines, Cervarix and Gardasil. Cervarix includes monophosphoryl lipid A and an aluminum adjuvant, and it significantly increased the expression of IL-6 and IFN-ß mRNAs in RAW264.7 cells. On the contrary, Gardasil, which only includes an aluminum adjuvant, exhibited little cytokine expression but increased the expression of TLRs. Furthermore, Cervarix significantly increased IL-1ß secretion from mouse macrophages, while Gardasil only mildly induced IL-1ß secretion. Interestingly, initial stimulation with Gardasil enhanced the expression of IL-6 and TNF-α mRNAs upon secondary stimulation with TLR ligands, indicating that Gardasil induced trained immunity in macrophages. Moreover, Gardasil injection into mice resulted in enhanced TNF-α production in sera following secondary TLR stimulation. Our findings suggest that HPV vaccinations have the ability to induce trained immunity that modulate TLR ligand responses.

Cost-effectiveness of human papillomavirus (HPV) vaccination in Burkina Faso: a modelling study.

BACKGROUND: Africa has some of the highest cervical cancer incidence and mortality rates globally. Burkina Faso launched a human papillomavirus (HPV) vaccination programme for 9-year-old girls in 2022 with support from Gavi, the Vaccine Alliance (Gavi). An economic evaluation of HPV vaccination is required to help sustain investment and inform decisions about optimal HPV vaccine choices. METHODS: We used a proportionate outcomes static cohort model to evaluate the potential impact and cost-effectiveness of HPV vaccination for 9-year-old girls over a ten-year period (2022-2031) in Burkina Faso. The primary outcome measure was the cost (2022 US$) per disability-adjusted life year (DALY) averted from a limited societal perspective (including all vaccine costs borne by the government and Gavi, radiation therapy costs borne by the government, and all other direct medical costs borne by patients and their families). We evaluated four vaccines (CERVARIX®, CECOLIN®, GARDASIL-4®, GARDASIL-9®), comparing each to no vaccination (and no change in existing cervical cancer screening and treatment strategies) and to each other. We combined local estimates of HPV type distribution, healthcare costs, vaccine coverage and costs with GLOBOCAN 2020 disease burden data and clinical trial efficacy data. We ran deterministic and probabilistic uncertainty analyses. RESULTS: HPV vaccination could prevent 37-72% of cervical cancer cases and deaths. CECOLIN® had the most favourable cost-effectiveness (cost per DALY averted < 0.27 times the national gross domestic product [GDP] per capita). When cross-protection was included, CECOLIN® remained the most cost-effective (cost per DALY averted < 0.20 times the national GDP per capita), but CERVARIX® provided greater health benefits (66% vs. 48% reduction in cervical cancer cases and deaths) with similar cost-effectiveness (cost per DALY averted < 0.28 times the national GDP per capita, with CECOLIN® as the comparator). We estimated the annual cost of the vaccination programme at US$ 2.9, 4.1, 4.4 and 19.8 million for CECOLIN®, GARDASIL-4®, CERVARIX® and GARDASIL-9®, respectively. A single dose strategy reduced costs and improved cost-effectiveness by more than half. CONCLUSION: HPV vaccination is cost-effective in Burkina Faso from a limited societal perspective. A single dose strategy and/or alternative Gavi-supported HPV vaccines could further improve cost-effectiveness.

Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

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.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

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 aimed to  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 have no 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.

Impact, cost-effectiveness, and budget implications of HPV vaccination in Kenya: A modelling study.

BACKGROUND: Sub-Saharan Africa has the highest rate of cervical cancer cases and deaths worldwide. Kenya introduced a quadrivalent HPV vaccine (GARDASIL, hereafter referred to as GARDASIL-4) for ten-year-old girls in late 2019 with donor support from Gavi, the Vaccine Alliance. As Kenya may soon graduate from Gavi support, it is important to evaluate the potential cost-effectiveness and budget impact of the current HPV vaccine, and potential alternatives. METHODS: We used a proportionate outcomes static cohort model to evaluate the annual budget impact and lifetime cost-effectiveness of vaccinating ten-year-old girls over the period 2020-2029. We included a catch-up campaign for girls aged 11-14 years in 2020. We estimated cervical cancer cases, deaths, disability adjusted life years (DALYs), and healthcare costs (government and societal perspective) expected to occur with and without vaccination over the lifetimes of each cohort of vaccinated girls. For each of the four products available globally (CECOLIN©, CERVARIX©, GARDASIL-4©, and GARDASIL-9 ©), we estimated the cost (2021 US$) per DALY averted compared to no vaccine and to each other. Model inputs were obtained from published sources, as well as local stakeholders. RESULTS: We estimated 320,000 cases and 225,000 deaths attributed to cervical cancer over the lifetimes of the 14 evaluated birth cohorts. HPV vaccination could reduce this burden by 42-60 %. Without cross-protection, CECOLIN had the lowest net cost and most attractive cost-effectiveness. With cross-protection, CERVARIX was the most cost-effective. Under either scenario the most cost-effective vaccine had a 100 % probability of being cost-effective at a willingness-to-pay threshold of US$ 100 (5 % of Kenya's national gross domestic product per capita) compared to no vaccination. Should Kenya reach its target of 90 % coverage and graduate from Gavi support, the undiscounted annual vaccine program cost could exceed US$ 10 million per year. For all three vaccines currently supported by Gavi, a single-dose strategy would be cost-saving compared to no vaccination. CONCLUSION: HPV vaccination for girls is highly cost-effective in Kenya. Compared to GARDASIL-4, alternative products could provide similar or greater health benefits at lower net costs. Substantial government funding will be required to reach and sustain coverage targets as Kenya graduates from Gavi support. A single dose strategy is likely to have similar benefits for less cost.

Chimeric Human Papillomavirus-16 Virus-like Particles Presenting HIV-1 P18I10 Peptide: Expression, Purification, Bio-Physical Properties and Immunogenicity in BALB/c Mice.

Human papillomavirus (HPV) vaccines based on HPV L1 virus-like particles (VLPs) are already licensed but not accessible worldwide. About 38.0 million people were living with HIV in 2020 and there is no HIV vaccine yet. Therefore, safe, effective, and affordable vaccines against both viruses are an urgent need. In this study, the HIV-1 P18I10 CTL peptide from the V3 loop of HIV-1 gp120 glycoprotein was inserted into the HPV16 L1 protein to construct chimeric HPV:HIV (L1:P18I10) VLPs. Instead of the traditional baculovirus expression vector/insect cell (BEVS/IC) system, we established an alternative mammalian 293F cell-based expression system using cost-effective polyethylenimine-mediated transfection for L1:P18I10 protein production. Compared with conventional ultracentrifugation, we optimized a novel chromatographic purification method which could significantly increase L1:P18I10 VLP recovery (~56%). Chimeric L1:P18I10 VLPs purified from both methods were capable of self-assembling to integral particles and shared similar biophysical and morphological properties. After BALB/c mice immunization with 293F cell-derived and chromatography-purified L1:P18I10 VLPs, almost the same titer of anti-L1 IgG (p = 0.6409) was observed as Gardasil anti-HPV vaccine-immunized mice. Significant titers of anti-P18I10 binding antibodies (p < 0.01%) and P18I10-specific IFN-γ secreting splenocytes (p = 0.0002) were detected in L1:P18I10 VLP-immunized mice in comparison with licensed Gardasil-9 HPV vaccine. Furthermore, we demonstrated that insertion of HIV-1 P18I10 peptide into HPV16 L1 capsid protein did not affect the induction in anti-L1 antibodies. All in all, we expected that the mammalian cell expression system and chromatographic purification methods could be time-saving, cost-effective, scalable platforms to engineer bivalent VLP-based vaccines against HPV and HIV-1.

Human papillomavirus (HPV) vaccines in adults: Learnings from long-term follow-up of quadrivalent HPV vaccine clinical trials.

The risk for acquiring human papillomavirus (HPV) infections and associated diseases is lifelong. An important part of prophylactic HPV vaccine development is durable protection against infection and disease. With comprehensive long-term follow-up (LTFU) in adolescents, men, and women, the quadrivalent HPV (qHPV) vaccine demonstrated durable effectiveness, immunogenicity, and safety, with almost no breakthrough disease. Those who received a placebo during initial trials were offered the qHPV vaccine at study conclusion and continued to be followed in LTFU extensions. In this catch-up vaccination group, LTFU demonstrated protection even in individuals with current or prior HPV infection after approximately 3 years. The initial efficacy and durable long-term effectiveness of the qHPV vaccine have already translated to a real-world reduction in cancer and cancer precursors. To date, there is no evidence of waning protection; evidence suggests that vaccination ultimately provides strong protection against future disease, with effective prophylaxis even among those with past infections.

Immunogenicity of a quadrivalent human papillomavirus vaccine in pediatric kidney and liver transplant recipients.

BACKGROUND: Solid-organ transplant recipients are at increased risk of developing human papillomavirus-related diseases. METHODS: To evaluate the immunogenicity of a quadrivalent vaccine, a prospective observational study included females aged 12-19 years who had received kidney or liver transplants, or were otherwise healthy volunteers. With the three-dose vaccination, serum antibodies were measured. RESULTS: The study included 17 transplant recipients (seven kidney and 10 liver) and 16 healthy participants. Six of seven kidney transplant recipients were on three immunosuppressive medications, whereas 9 of the 10 liver transplant recipients were on one. For the serology within 6 months from the last vaccine dose, the geometric mean titers of human papillomavirus types 6, 11, 16, and 18 were 26.7, 8.6, 35.7, and 42.4 (kidney transplant); 579.2, 569.3, 3097.3, and 835.7 (liver transplant); and 860.5, 638.8, 4391.6, and 902.6 milli-Merck Units/ml (healthy). The seropositivity rates of kidney transplant recipients for the four serotypes ranged from 50% to 75%, while all liver transplant recipients and healthy participants had 100% seropositivity rates for all four types. While there were no statistical differences of titers between liver transplant recipients and healthy participants, the titers of kidney transplant recipients were lower than those of healthy participants for type 6 (p = .034), type 11 (p = .032), and type 16 (p = .032). CONCLUSIONS: The results support the recommendation of human papillomavirus vaccination in pediatric transplant recipients given the significant risk of human papillomavirus-related diseases in this population, though immunogenicity was lower in kidney transplant recipients on multiple immunosuppressive medications.

Human papillomavirus vaccination in Africa: An airway perspective.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic condition caused by Human papillomavirus six (HPV-6) and HPV-11 that involves the respiratory tract. Disease severity ranges from mild (hoarseness), through to severe (stridor, respiratory distress and airway emergencies). Africa has the fastest growing and youngest population of all the continents. It also has the greatest burden of cervical cancer. There is an association with infection of the oncogenic HPV strains and the strains responsible for RRP. It is reasonable to conclude that although RRP may be underestimated in low-to-middle-income countries, it poses a considerable health risk to Africa. The primary aim of this project was to assess the suitability of HPV vaccination coverage on the African continent. METHODS: A prospective study was designed to consist of an online survey. It was distributed to 135 African otolaryngologists. Questions focussed on HPV vaccination programmes; whether they were government directed; and their rollout. Information from countries that had multiple otolaryngologists respond to the survey were compared. Additionally, data review and corroboration were performed. RESULTS: There were 58 (43%) participants from 19 countries. Nine countries reported a national vaccination programme (NVP), five used Cervarix; four used quadrivalent Gardasil. Collateral data revealed 18 of 54 countries had NVP in Africa and 26 countries had completed HPV vaccine pilot or demonstration projects. CONCLUSIONS: HPV vaccination in Africa should be urgently re-evaluated to include the HPV-6 and HPV-11 strains that cause JORRP, which have not been recognised during national vaccination programme planning.

The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis.

OBJECTIVE: To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). DATA SOURCES: PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021. REVIEW METHODS: All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination. RESULTS: The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, -7.48 to -1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46-29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination. CONCLUSION: The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2046-2054, 2023.

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.

BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Incident autoimmune conditions among males receiving quadrivalent human papillomavirus vaccine in the United States.

BACKGROUND: The potential for vaccines to induce autoimmunity has been the subject of considerable investigation and autoimmune induction remains a common focus for vaccine safety research. This study assessed the risk of new onset autoimmune conditions among males receiving the 4-valent human papillomavirus (HPV) vaccine (4vHPV). METHODS: Within a US health insurance claims database, we formed a cohort of male 4vHPV vaccine recipients between 2009 and 2016, along with a propensity score matched cohort of males who did not receive the 4vHPV vaccine. The study outcome was new onset autoimmune conditions (20 separate conditions) within four categories (rheumatologic/hematologic, gastroenterologic, endocrinologic and neurologic/ophthalmalogic). Outcomes identified using diagnosis codes were adjudicated through medical record review. Incidence rates (per 1,000 person-years) were estimated for the vaccinated and unvaccinated groups along with rate ratios (RRs). RESULTS: There were 65,606 males receiving at least one dose of 4vHPV vaccine, and 55,670 were matched to a comparator. The matched 4vHPV vaccine cohort provided 35 confirmed cases among 39,735 person-years, for an incidence rate of 0.88 (95% CI: 0.61-1.23), while the comparator cohort provided 47 confirmed cases among 58,215 person-years, an incidence rate of 0.81 (0.59-1.07), a RR of 1.09 (0.70-1.69). The RR within categories was 0.49 (0.10-2.42) for rheumatologic/hematologic, 1.26 (0.58-2.71) for gastroenterologic, 1.11 (0.61-2.02) for endocrinologic and 1.46 (0.21-10.40) for neurologic. CONCLUSIONS: The incidence of autoimmune conditions among males receiving the 4vHPV vaccine was similar to that among unvaccinated males. These results are consistent with other studies that have assessed autoimmunity with the 4vHPV vaccine.