The Male Voice: A Qualitative Assessment of Young Men's Communication Preferences About HPV and 9vHPV.

In the U.S. there is an epidemic of sexually transmitted diseases (STIs). One of the most prevalent STIs is the Human Papillomavirus (HPV). Certain high risk strains of HPV are believed to cause virtually all cervical cancers, over 90% of anal cancers, 70% of oropharyngeal cancers, and the majority of anal genital warts. HPV is preventable through vaccination and is available for both men and women. Several educational interventions have been employed, yet baseline awareness and knowledge related to HPV and 9vHPV remains relatively low among young men. What is not known is the most effective method for providing HPV and 9vHPV information to young men. The purpose of this qualitative study was to learn from young men on how they would like to receive HPV and 9vHPV information. Men between the ages of 18-26 were invited to participate in the study. Ten focus group sessions with a total of 68 participants were conducted from three Midwest community colleges. Analysis resulted in themes related to STIs, HPV and 9vHPV knowledge, 9vHPV receipt, sexual health communication, and communication strategies. Findings suggest that there is not a "one size fits all" preferred communication modality. Recommendations for effective HPV communication include healthcare practitioner self-awareness, community environments where healthcare practitioners can engage in HPV related cancer prevention activities and advocacy for medically accurate sexual health education. Insight into the best way to communicate HPV and 9vHPV information to young men will lead toward improvement in health literacy around HPV, increased 9vHPV uptake, as well as effective health promotion and disease prevention.

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix in Healthy Adolescents: A Randomized Phase IIIb Multicenter Study.

INTRODUCTION: Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents. METHODS: In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status. RESULTS: A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified. CONCLUSIONS: These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents. TRIAL REGISTRATIONS: Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.

MenACYW conjugate vaccine has been made to protect against meningococcal disease caused by four common types of bacteria (germs) called Neisseria meningitidis (or meningococcus), A, C, W, and Y. Many people, particularly adolescents, have the germs of this disease in their nose or throat, and therefore may develop the disease or transmit the bacteria to other people. Hence, adolescent meningococcal vaccination against serogroups ACWY is increasingly recommended in several countries. This study assessed the immune response to these serogroups in healthy adolescents after one dose of MenACYW conjugate vaccine or Nimenrix^®, a meningococcal licensed vaccine. Moreover, the immune response and safety were assessed when the vaccines were given alone or when given concomitantly with other adolescent vaccines, including the human papillomavirus (9vHPV) and tetanus, diphtheria, pertussis, and poliomyelitis (Tdap-IPV) vaccines. A total of 463 adolescents (aged 10­17 years) participated in this study and received either MenACYW or Nimenrix^® alone, or MenACYW concomitantly with 9vHPV and Tdap-IPV vaccine. The immune response induced by MenACYW was as good as the immune response induced by Nimenrix^®, and when given alone or concomitantly with 9vHPV and Tdap IPV vaccines. None of the participants experienced any serious side effects of any vaccine. The most common non-serious side effects were injection site pain, muscle pain, and headache. These data support the use of MenACYW in adolescents, with or without concomitant administration with 9vHPV and Tdap-IPV, which may help to increase the number of adolescents vaccinated.

HPV Opportunistic Vaccination: A Literature Review and a Single-Center Experience in Northern Italy through the COVID-19 Pandemic.

The World Health Organization (WHO) set the goal of 90% HPV vaccination coverage in the population to eliminate cervical cancer. Opportunistic vaccination is performed outside the free vaccination or catch-up programs. Both free and opportunistic HPV vaccination programs experienced slowdowns during the COVID-19 pandemic. In this retrospective study, we aimed to identify the benefits and the obstacles of opportunistic vaccination among male and female individuals who took advantage of the "on-demand" service offered by San Raffaele Hospital in Milan from April 2018 to May 2023. The impact that the COVID-19 pandemic had on vaccination adherence was also analyzed. Data on a total of 527 subjects were collected from an in-house database and through personal interviews. Women in the cohort of older patients (over 25) adhered to the vaccination schedule more than younger women. Opportunistic vaccination request is influenced by the need of a gynecologist, a general practitioner, or public health clinic availability. Women also showed good adherence to screening, demonstrating awareness of the importance of cervical cancer secondary prevention despite vaccination. Opportunistic vaccination offers the possibility of including individuals excluded from the free vaccination campaigns, often already affected by lesions caused by HPV, providing increased viral clearance and faster lesion regression. The main limit remains the economic burden.

HPV and Cytology Testing in Women Undergoing 9-Valent HPV Opportunistic Vaccination: A Single-Cohort Follow Up Study.

Background: This study evaluates the possible effect of 9-valent (9vHPV) vaccination on the results of HPV and cytological tests in a cohort of adult women. Methods: This study is a retrospective, single-cohort, monocentric study. Sexually active women aged 14-70 years, who underwent 9vHPV vaccination, were enrolled. Dose administration dates, side effects and data on Pap smears and HPV tests performed before and after the first vaccine dose were collected. Subjects were considered "unexposed" to the vaccine for all time intervals before the first dose administration, and "exposed" to the first, second and third vaccine doses in all time intervals following each specific dose. Results: A total of 512 women underwent the first 9vHPV dose administration and were enrolled in the study. Median age at vaccination was 30.5 (14-70). Log-rank tests and Cox regression analyses showed a highly statistically significant (p < 0.0001) difference in the time to negativization after the exposure to the third vaccine dose in the 207 women starting with a Pap+ smear (HR (95% C.I.), 2.66 (1.83-3.86)) and in the 198 women starting with an HPV HR+ test (HR (95% C.I.), 7.80 (4.83-12.60)). Conclusions: 9vHPV vaccination may play a role in shortening the clearance time of HPV HR+ or Pap positivity in sexually active adult women.

Portrayals of 2v, 4v and 9vHPV vaccines on Chinese social media: a content analysis of hot posts on Sina Weibo.

Rather than receive the effective 2vHPV vaccines that are readily available in China, Chinese women usually wait to receive 4v and 9vHPV vaccines, which are difficult to acquire. This means that Chinese women miss the opportunity for optimal protection from cervical cancer. As social media platforms are the main channel by which Chinese women learn about HPV vaccines, this study aimed to explore how HPV vaccines are described on social media, and in particular how they discuss or distinguish 2 v, 4 v and 9vHPV vaccines. The Octopus Web crawler tool was used to capture hot Weibo posts from 2013-2021, and 1,164 valid data were obtained. Results suggested that there are very few posts with great influence on Weibo about HPV vaccines among 9 years and much of them are created by "lay people." HPV-related topics lacked persistent popularity, comprised highly repetitive content and the spread of information was geographically diverse. There were significant differences in the media descriptions of different kinds of HPV vaccines. Price was mentioned more often in the descriptions of 2vHPV vaccines, whereas appointments were referred to most often in the descriptions of 9vHPV vaccines. There was little media attention paid to the safety and effectiveness of HPV vaccines. Chinese media should develop better collaborations with public health professionals, pay more attention to the originality of their news coverage of HPV vaccines and strive to promote HPV vaccination. Such collaboration will help news media to better understand the key points of HPV information that need to be disseminated.

Human papillomavirus vaccination uptake in low-and middle-income countries: a meta-analysis.

BACKGROUND: The proportion of incident cases of HPV-attributable cancers is highest in the low- and middle-income countries (LMICs) but many are yet to initiate HPV vaccination programs. This meta-analysis was performed to assess the uptake of HPV vaccination in LMICs at the beginning of the global strategy to eliminate cervical cancer and describes the gaps and challenges. METHODS: A systematic search was conducted in PubMed, EMBASE, Scopus, Web of Science, and CENTRAL databases for observational studies that reported the uptake of HPV vaccination until October 2020. The meta-analysis was done using a random-effects model to assess the pooled estimate of HPV uptake. CRD42021218429. FINDINGS: During 2008-2020, an estimated 3.3 million females received at least one dose of HPV vaccine with 61.69% of the target population vaccinated. In countries with high uptake, the pooled estimate of uptake was higher in females than males (45.48% vs 8.45%) and showed significant decline in 2015-2020 compared to 2006-2014 (89.03% vs 41.48%). In countries with low uptake, the estimate of uptake was low in both males and females (5.31% vs 2.93%) and showed increase in uptake in 2015-2020 compared to 2006-2014 (0.76% vs 5.22%). In countries with high uptake, compared to routine programs, the estimate was higher when delivered through demonstration programs (89.94% vs 59.74%). INTERPRETATION: The major concern was a significant drop in the uptake in countries that started with high uptake, challenges in the maintenance of vaccine uptake, sustainability of funding and the lack of standard monitoring and reporting.

Evaluation of Human Papillomavirus Vaccination After Pharmacist-Led Intervention: A Pilot Project in an Ambulatory Clinic at a Large Academic Urban Medical Center.

OBJECTIVES: Despite the safety and efficacy of the human papillomavirus (HPV) vaccine, many persons are still not receiving it. The purpose of this pilot project was to evaluate the number of first doses of the 9-valent HPV (9vHPV) vaccination administered after a pharmacist-led intervention in the Adult Family Planning Clinic at Grady Health System (GHS), a large academic urban medical center in Atlanta, Georgia. METHODS: The pilot project had 3 phases: pre-intervention (November 15, 2016, through March 31, 2017), active intervention (November 15, 2017, through December 29, 2017), and post-intervention (December 30, 2017, through March 31, 2018). The pre-intervention phase was used as a historical control. The active intervention phase consisted of pharmacist interventions in the clinic and patient and health care provider education. The post-intervention phase evaluated the durability of pharmacist-led interventions performed and education provided during the active phase. RESULTS: Eighty-nine first-dose 9vHPV vaccines (of the 3-dose series) were administered to young adults aged 18-26 during the project period (November 15, 2017, through March 31, 2018); none were administered during the pre-intervention phase. Of 89 patients who received a first 9vHPV vaccine dose, 20 patients also received a second 9vHPV vaccine dose. During the project period, 166 doses of 9vHPV vaccine (first, second, or third doses) were administered. CONCLUSION: This pharmacist-led intervention led to an increase in the number of young adult patients receiving their first dose of the 9vHPV vaccination series. With the support of other health care providers, pharmacist-led initiatives can expand vaccine-related health literacy and facilitate access to immunization services.

Investigation on Spontaneous Abortion and Human Papillomavirus Infection.

Viral infections are considered to be risk factors for spontaneous abortion (SA). Conflicting results have been reported on the association between Human Papillomavirus (HPV) and SA. HPV DNA was investigated in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from women who experienced SA (n = 80, cases) and women who underwent a voluntary interruption of pregnancy (VI; n = 80, controls) by qualitative PCR and quantitative droplet digital PCR (ddPCR). Viral genotyping was performed using real-time PCR in HPV-positive samples. Specific IgG antibodies against HPV16 were investigated in sera from SA (n = 80) and VI (n = 80) females using indirect ELISA assays. None of the DNA samples from SA subjects was HPV-positive (0/80), whilst HPV DNA was detected in 2.5% of VI women (p > 0.05), with a mean viral DNA load of 7.12 copy/cell. VI samples (n = 2) were found to be positive for the HPV45 genotype. The ddPCR assay revealed a higher number of HPV-positive samples. HPV DNA was detected in 3.7% and 5% of SA and VI chorionic tissues, respectively, with mean viral DNA loads of 0.13 copy/cell in SA and 1.79 copy/cell in VI (p >0.05) samples. All DNA samples from the PBMCs of SA and VI females tested HPV-negative by both PCR and ddPCR. The overall prevalence of serum anti-HPV16 IgG antibodies was 37.5% in SA and 30% in VI (p > 0.05) women. For the first time, HPV DNA was detected and quantitatively analyzed using ddPCR in chorionic villi tissues and PBMCs from SA and VI women. Circulating IgG antibodies against HPV16 were detected in sera from SA and VI females. Our results suggest that HPV infection in chorionic villi may be a rare event. Accordingly, it is likely that HPV has no significant role in SA.

Maternal transfer of anti HPV 6 and 11 antibodies upon immunization with the 9-valent HPV vaccine.

BACKGROUND: This exploratory analysis was conducted to characterize the level of HPV types 6/11 antibodies in peripartum maternal blood and in cord blood of infants born to women who received 9-valent HPV (9vHPV) vaccine or quadrivalent HPV (qHPV) vaccine in a pivotal efficacy study (V503-001, NCT 00543543). METHODS: A total of 21 mother-infant pairs had evaluable HPV 6/11 results available for analysis. HPV6/11 antibodies were assessed using competitive Luminex immunoassay. The distribution of the ratios of infant to mother anti-HPV antibodies (i.e., infant-anti-HPV/mother- anti-HPV) was summarized. RESULTS: All mothers and infants were seropositive to HPV 6 and HPV 11. Anti-HPV 6/11 geometric mean titers (GMTs) in peripartum maternal blood and in cord blood of infant born to study participants were highly correlated. A 100% of infants born to seropositive mothers were also seropositive. The GMT ratios of peripartum maternal blood vs. those in cord blood were HPV 6: 1.23 [0.43, 3.49] and HPV 11: 1.29 [0.54, 3.07] in the 9vHPV vaccine group and HPV 6: 1.33 [0.41, 4.29] and HPV 11: 1.19 [0.45, 3.13] in the qHPV vaccine group, respectively. CONCLUSIONS: These results indicate that antibodies induced by the 9vHPV vaccine cross the placenta, which could potentially be beneficial against HPV6/11 infection and related disease such as recurrent respiratory papillomatosis.

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age.

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

BACKGROUND: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. METHODS: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. RESULTS: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. CONCLUSIONS: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden.

Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine.

The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets four HPV types (6/11/16/18) also covered by the quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). Vaccine efficacy to prevent HPV infection and disease was established in a Phase III clinical study in women 16-26years of age. A long-term follow-up (LTFU) study has been initiated as an extension of the Phase III clinical study to assess effectiveness of the 9vHPV vaccine up to at least 14years after the start of vaccination. It includes participants from Denmark, Norway and Sweden and uses national health registries from these countries to assess incidence of cervical pre-cancers and cancers due to the 7 oncogenic types in the vaccine (HPV 16/18/31/33/45/52/58). Incidences will be compared to the estimated incidence rate in an unvaccinated cohort of similar age and risk level. This LTFU study uses a unique design: it is an extension of a Phase III clinical study and also has elements of an epidemiological study (i.e., endpoints based on standard clinical practice; surveillance using searches from health registries); it uses a control chart method to determine whether vaccine effectiveness may be waning. Control chart methods which were developed in industrial and manufacturing settings for process and production monitoring, can be used to monitor disease incidence in real-time and promptly detect a decrease in vaccine effectiveness. Experience from this innovative study design may be applicable to other medicinal products when long-term outcomes need to be assessed, there is no control group, or outcomes are rare.

Antibody persistence and evidence of immune memory at 5years following administration of the 9-valent HPV vaccine.

BACKGROUND: The 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5years post-vaccination. METHODS: A subset of subjects (N=150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card. RESULTS: HPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1week and 1month post-dose 4 were 1.25-4.10 and 1.65-4.88-fold higher, respectively, than levels observed 1month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1week and 1month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated. CONCLUSIONS: A three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting. Clinical Trials.gov Identifier:NCT00543543.