Potential impact of a nonavalent anti HPV vaccine in Italian men with and without clinical manifestations.

Human papilloma virus infection (HPV) is the most common sexually transmitted disease. Little is known about male infection. Nonavalent vaccine against types 6/11/16/18/31/33/45/52/58 was approved and neutral gender immunization programs have been proposed. This study evaluates the potential impact of nonavalent vaccine compared to quadrivalent in male living in Sicily (Italy). 58.7% of samples were HPV positive and forty-four types of HPV were identified. A significant higher estimated coverage of nonavalent vaccine than quadrivalent was observed (64.3% vs. 45.8%), with absolute and relative additional impact of 20.1% and 47.2%, respectively. Low impact of the vaccine were calculated as the empirical probability of HPV genotypes 6/11/16/18/31/33/45/52/58 alone or in combination; the high impact as empirical probability of HPV6/11/16/18/31/33/45/52/58 genotypes alone or in association with other genotypes. The potential impact of the nonavalent vaccine vs quadrivalent was significant for low and high impact (29.7% > 18:8%; 34:6% > 26.6%, respectively). Particularly, in men with lesions and risky sexual contact was significant only for low impact (35.5% > 29.7%; 31.4% > 19.7%, respectively). In partners with positive females was significant for low impact (26.3% > 15.1%) and high impact (33.7% > 23.2%). Nonavalent vaccine offers broader protection in men with HPV positive partners, who would have a potential role in the transmission of the infection.

Case Report: Intra-Tumoral Vaccinations of Quadrivalent HPV-L1 Peptide Vaccine With Topical TLR-7 Agonist Following Recurrence: Complete Resolution of HPV-HR-Associated Gynecologic Squamous Cell Carcinomas in Two Patients.

The human papilloma virus (HPV) high-risk variants (HPV-HR) such as HPV16 and HPV18 are responsible for most HPV related cancers, including anogenital and head and neck cancers. Here, we present two patients with HPV-HR-associated gynecological malignancies who, after failing radiation therapy, were treated with experimental salvage immunotherapy regimen resulting in complete, durable responses in both patients. Each patient was diagnosed with recurrent, radiation-refractory, HPV-HR positive, squamous cell carcinoma of the lower genital tract. Patient A was a 90-year-old, African American, with metastatic vulvar cancer to the right inguinal-femoral triangle and pulmonary metastases. Patient B was a 41-year-old, Caucasian, with a central-recurrence of cervix cancer. Each patient received at least two intratumoral quadrivalent HPV-L1 vaccine (Gardasil™) injections and daily topical TLR-7 agonist (imiquimod) to the tumor surface 2 weeks apart. This combination of intratumoral vaccinations and topical TLR-7 agonist produced unexpected complete resolution of disease in both patients. The importance of radiation therapy, despite being considered a treatment failure by current definitions, cannot be understated. Radiation therapy appears to have offered a therapeutic immune advantage by modifying the tumor microenvironment. This immune protocol has potential to help patients with advanced HPV-HR-related malignancies previously considered incurable.

Human Papillomavirus (HPV) and the quadrivalent HPV Vaccine among Brazilian adolescents and parents: Factors associated with and divergences in knowledge and acceptance.

BACKGROUND: Low national immunization coverage (44.64%) requires strengthening the vaccination campaign to improve knowledge about HPV and its vaccine among adolescents and parents/guardians. Our aim is to evaluate factors related to knowledge about HPV, its vaccine, acceptability and divergences among Brazilian adolescents and parents/guardians. METHODS: A cross-sectional study was performed at a health unit of Sao Paulo University, Brazil, from 2015 to 2016. The convenience sample comprised 1047 individuals, including 74% (n = 776) adolescents and 26% (n = 271) parents/guardians, who answered a survey (knowledge about HPV, its vaccine, barriers and acceptability). RESULTS: The main source of information for adolescents was school (39%, n = 298); for parents/guardians, it was health professionals (55%, n = 153). Parents/guardians were 2.48 times more likely than adolescents to know that HPV caused changes in the Pap smear test [RR 2.48, 95% CI 2.03-3.01 (p < 0.001)], 1.43 times likely to be aware that HPV was a sexually transmitted infection [RR 1.43, 95% CI 1.22-1.68 (p < 0.001)], and 2.77 times likely to be informed that the HPV vaccine decreased the chance of having genital warts [RR 2.77, 95% CI 2.22-2.47 (p < 0.001)]. Girls knew more about the topic than boys (RR 1.67; 95% CI 1.10-2.60); education increased parents' knowledge [(RR 3.38; 95% CI 1.71-6.69)]. CONCLUSION: Female adolescents and parents/guardians with a higher level of education are factors related to suitable knowledge about HPV and its vaccine among Brazilian respondents. There were differences between parents/guardians and adolescents in HPV awareness, clinical implications, vaccine knowledge and vaccine acceptance.

Vacuna contra virus del papiloma humano (VPH) en pacientes con lesiones o infección por VPH / Human papillomavirus (HPV) vaccine in patients with HPV lesions or infection

CONTEXTO CLÍNICO: El cáncer de cuello uterino es un importante problema de salud pública a nivel mundial. El mismo ocupa el quinto lugar en frecuencia en todo el mundo. Las estadísticas mundiales provistas por GLOBOCAN de 2018 muestran una tasa de incidencia de cáncer de cuello de útero, estandarizada por edad y sexo, de 13,1 por 100.000 personas-año. Según datos de la IARC (del inglés International Agency for Research on Cancer), el número de muertes estimada en Argentina para este tipo de cáncer en 2018 fue de 2.231, mientras que su incidencia se estimó en 4.484, siendo el Noreste la región del país con mayor incidencia. Aproximadamente 33.700 casos de cáncer son causados por el virus del papiloma humano (VPH) en los Estados Unidos cada año; incluyendo 12.900 con localización orofaríngea, 10.800 en cuello de uterino y 6.000 casos de cáncer anal en hombres y mujeres; mientras que el cáncer de vagina, vulva y pene son menos frecuentes. TECNOLOGÍA: Actualmente hay tres vacunas autorizadas por FDA, EMA (del inglés European Medicines Agency) y ANMAT (Administración Nacional Medicamentos, Alimentos y Tecnología Médica) contra el VPH: uma bivalente contra los tipos oncogénicos de VPH 16 y 18 (Cervarix®), otra cuadrivalente contra VPH 16, 18 y los genotipos 6 y 11 los cuales son agentes causales de verrugas genitales (Gardasil®), y uma nonavalente que protege contra los genotipos incluidos en la cuadrivalente y cinco más: HPV 31, 33, 45, 52 y 58 (Gardasil 9®). Las vacunas son recombinantes, no infecciosas, adyuvadas y preparadas a partir de la proteína principal de la cápside L1 y altamente purificadas. Puesto que no contienen ADN viral, no pueden infectar células, reproducirse o causar enfermedad. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de la vacuna contra el virus del papiloma humano para pacientes de ambos sexos con infecciones o lesiones pre-existentes de VPH. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron un ECA, dos análisis post- hoc de ECAs, dos estudios observacionales, dos RS, cuatro GPC y 11 informes de políticas de cobertura acerca de la vacuna contra el virus del papiloma humano (VPH) en pacientes con lesiones o infección por VPH. CONCLUSIONES: La vacuna contra el virus del papiloma humano cuenta con la aprobación por ANMAT (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica) para su indicación a partir de los 9 años, y forma parte del Calendario Nacional de vacunación para su indicación a los 11 años. Este documento evalúa el uso de la vacuna en pacientes con lesiones o infección por el virus pre-existentes a la vacunación (población no incluida específicamente en el prospecto -un uso "off-label"). No se encontraron estudios que evalúen la eficacia de la vacuna en disminuir la mortalidad o incidencia de cáncer en pacientes con lesiones o infección por el virus pre-existentes a la vacunación. Evidencia de moderada calidad sugiere que la vacunación contra el virus del papiloma humano es superior al placebo en prevenir la recidiva de neoplasias cervicales intraepiteliales grado 2 o más severas, en pacientes con antecedentes de dichas lesiones diagnosticadas y tratadas previamente a la vacunación. Evidencia de baja calidad sugiere que la tecnología podría reducir las recurrencias de lesiones intraepiteliales anales, vulvares y vaginales. Evidencia de muy baja calidad no permite concluir acerca de los beneficios de la vacunación en pacientes con papilomatosis respiratoria recurrente. Evidencia de moderada calidad sugiere que la vacunación en pacientes sin antecedentes de lesiones pre-malignas pero con ADN positivo y/o serología positiva para el virus del papiloma humano, no presenta claros beneficios en la prevención del desarrollo de lesiones de cuello de útero, anales y orales, pudiendo tener algún beneficio en disminuir la incidencia de infecciones nuevas por algunos genotipos del virus. De todas formas, ninguna de las recomendaciones internacionales recomienda la detección de infección viral previa a la vacunación. Las guías de práctica clínica y recomendaciones de inmunizaciones relevadas recomiendan la vacunación en todas las personas entre los 11 (pudiendo comenzar a los 9 años) y 26 años; predominantemente a los 11 años, previo al contacto con el virus. La mayoría de ellas recomenda la toma de decisiones médicas compartidas, evaluando cada caso en particular, en personas entre 27 y 45 años, especialmente en pacientes con factores de riesgo para contraer una nueva infección. Los financiadores públicos de Estados Unidos, del Reino Unido y de Latinoamérica no hacen mención a la indicación de la vacunación en pacientes con lesiones o infecciones previas por el virus. Financiadores privados de Estados Unidos consideran a la vacuna experimental para estas indicaciones, aunque alguno contempla la cobertura en casos seleccionados. No se encontraron estudios económicos locales acerca de la costo-efectividad de esta tecnologia en las indicaciones evaluadas.

The human papillomavirus vaccine as a treatment for human papillomavirus-related dysplastic and neoplastic conditions: A literature review.

BACKGROUND: Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE: To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS: A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS: A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS: This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION: The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

What Have We Missed?: The Knowledge of and Access to the HPV Vaccine and Sex Education in China.

The author completed three doses of Gardasil vaccine, which helps to protect against diseases caused by HPV (genital human papillomavirus). The author, a woman born and raised in China, had no knowledge of HPV or the HPV vaccine until she came to the United States for graduate school. In this piece, she presents a personal intercultural medical story about her HPV vaccine process. She utilizes personal narratives to share with readers her experience with sex education and to convey people's attitudes toward sexuality and sex education in mainland China.

Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status.

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006-2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow-up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow-up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HRadjusted = 0.86, 95% CI: 0.67-1.09). Women vaccinated 0-3 months before tended to have a slightly lower HR of CIN2+ (HRadjusted = 0.77, 95% CI: 0.45-1.32) than women vaccinated 0-12 months after conization (HRadjusted = 0.88, 95% CI: 0.67-1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high-grade cervical neoplasia to decrease risk of recurrence.

Cost-effectiveness and value-based prices of the 9-valent human papillomavirus vaccine for the prevention of cervical cancer in China: an economic modelling analysis.

OBJECTIVES: To evaluate the cost-effectiveness of the 9-valent human papillomavirus (HPV) vaccine for the prevention of cervical cancer in China. DESIGN: Health economic modelling using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model populated with China-specific data. SETTING: Individual cervical cancer prevention in China using the 9-valent HPV vaccine from the perspective of private sector purchasers in relation to receiving other HPV vaccines and not receiving vaccination for 16-year-old girls in China who had not been previously infected with HPV. PARTICIPANTS: Not applicable. INTERVENTIONS: Vaccination using the 9-valent, the quadrivalent and the bivalent vaccines. PRIMARY OUTCOME MEASURE: Incremental costs per disability-adjusted life year (DALY) prevented. RESULTS: In the base case, the incremental costs per DALY prevented were, respectively, US$35 000 and US$50 455 compared with the quadrivalent and the bivalent vaccines, both of which were above the cost-effective threshold of US$25 920/DALY prevented. To be cost-effective in these comparisons, the 9-valent vaccine should be priced at $550 and $450 for the full doses, respectively. To be highly cost-effective, the price thresholds were $435 and $335. The incremental costs per DALY prevented in relation to no vaccination was US$23 012, making the 9-valent vaccine marginally cost-effective. The results were robust in most one-way sensitivity analyses including changing vaccination age to 13 and 26 years. CONCLUSIONS: At the current price, the 9-valent HPV vaccine is not cost-effective compared with the quadrivalent and the bivalent vaccines for young girls in China who had not been previously infected with HPV. Policymakers and clinicians should keep potential vaccine recipients informed about the economic profile of the 9-valent vaccine and carefully consider expanding its use in China at the current price.

The cost-effectiveness of controlling cervical cancer using a new 9-valent human papillomavirus vaccine among school-aged girls in Australia.

INTRODUCTION: Cervical cancer imposes a substantial health burden worldwide including in Australia and is caused by persistent infection with one of 13 sexually transmitted high-risk human papillomavirus (HPV) types. The objective of this study was to assess the cost-effectiveness of adding a nonavalent new Gardasil-9® (9vHPV) vaccine to the national immunisation schedule in Australia across three different delivery strategies. MATERIALS AND METHODS: The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to examine the cost-effectiveness of 9vHPV vaccine introduction to prevent HPV infection. Academic literature and anecdotal evidence were included on the demographic variables, cervical cancer incidence and mortality, treatment costs, and vaccine delivery costs. The incremental cost-effectiveness ratios (ICERs) were measured per disability-adjusted life years (DALYs) averted, using the heuristic cost-effectiveness threshold defined by the World Health Organisation (WHO). Analyses and data from international agencies were used in scenario analysis from the health system and societal perspectives. RESULTS: The 9vHPV vaccination was estimated to prevent 113 new cases of cervical cancer (discounted) during a 20-year period. From the health system and societal perspectives, the 9vHPV vaccination was very cost-effective in comparison with the status quo, with an ICER of A$47,008 and A$44,678 per DALY averted, respectively, using the heuristic cost-effectiveness threshold level. Considering delivery strategies, the ICERs per DALY averted were A$47,605, A$46,682, and A$46,738 for school, health facilities, and outreach-based vaccination programs from the health system perspective, wherein, from the societal perspective, the ICERs per DALY averted were A$46,378, A$43,729, A$43,930, respectively. All estimates of ICERs fell below the threshold level (A$73,267). CONCLUSIONS: This cost-effectiveness evaluation suggests that the routine two-dose 9vHPV vaccination strategy of preadolescent girls against HPV is very cost-effective in Australia from both the health system and societal perspectives. If equally priced, the 9vHPV option is the most economically viable vaccine. Overall, this analysis seeks to contribute to an evidence-based recommendation about the new 9vHPV vaccination in the national immunisation program in Australia.

Implementation of Routine HPV Vaccination in the Management of Recurrent Respiratory Papillomatosis.

OBJECTIVES:: To investigate vaccine compliance and clinical outcomes after implementation of an initiative to provide the human papillomavirus (HPV) vaccine to all patients with recurrent respiratory papillomatosis (RRP). METHODS:: A retrospective review was performed of all adult patients treated for RRP from 2012 to 2017. Rates of HPV vaccination were evaluated before and after December 2015, when a program was established to increase compliance by educating patients and providing financial assistance toward vaccine administration. Paired sample analyses were conducted to compare intersurgical intervals (ISIs) and number of procedures per year pre- and post-vaccination. RESULTS:: Fourteen patients with RRP completed the HPV vaccine series, with 11 patients undergoing vaccination after the initiative began. The pre-initiative vaccination rate of all patients with RRP was 9.7%; post-initiative rates improved to 43.8% ( P = .004; odds ratio, 7.26). Of vaccinated patients, there were significant differences between mean pre-vaccine ISI (3.5 months) and post-vaccine ISI (12.8 months; P = .0021), as well as between number of surgical procedures performed per year before and after vaccination (2.7 vs 0.81; P = .014). After vaccination, 5 patients demonstrated no evidence of papilloma regrowth for >12 months. CONCLUSIONS:: Initiatives focused on patient education and financial support can successfully boost HPV vaccination rates in an RRP patient cohort. Our research mirrors prior findings that HPV vaccination is correlated with an increase in time between procedures and a decrease in number of procedures needed per year-factors that can dramatically reduce the disease burden on patients coping with RRP.

Squamous Cell Papillomatosis in the Setting of Recurrent Respiratory Papillomatosis.

A 23 year old male presented to the Otolaryngology clinic with 6 months of hoarseness and poor voice projection without improvement from speech therapy or medical anti-reflux medication. Upon examination he was found to have multiple polypoid lesions emanating from bilateral false vocal folds, left true vocal fold, and the anterior commissure. Biopsy and potassium titanyl phosphate (KTP) laser ablation with bevacizumab injection provided treatment and confirmed the clinical suspicion of squamous cell papilloma. Despite 3 years of treatment, the papillomatosis proved difficult to control, requiring a procedure approximately every 3 months. In an attempt to control the course of the disease the patient received a series of three bevacizumab and three cidofovir injections. Serial biopsies showed mild atypia within the squamous cell papillomas. Two separate biopsies confirmed presence of human papillomavirus (HPV) 6/11 via in situ hybridization with appropriate controls. There is promising research that the quadrivalent HPV (types 6, 11, 16, and 18) vaccine both reduces the disease burden in patients with active disease and reduces the incidence of recurrent respiratory papillomatosis (RRP). Other studies have shown that local immunologic dysregulation may play a role in RRP pathogenesis. Therefore new treatment options, to include PDL-1 blockade, offer hope in treating this benign condition with high morbidity and rare mortality.

Effectiveness of varying number of doses and timing between doses of quadrivalent HPV vaccine against severe cervical lesions.

BACKGROUND: Based on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule. METHODS: A population-based cohort of all women aged 13-30 years, living in Denmark or Sweden during 2006-2013, was followed for qHPV vaccination status and first occurrence of CIN2+. RESULTS: The study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13-16 and 17-19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11-0.49, and IRR = 0.65, 95% CI 0.41-1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13-16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses. CONCLUSIONS: Women vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.

Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges.

BACKGROUND: Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers. METHODS: Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24-41) and 6 mid-adult aged males (ages 27-45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA). RESULTS: All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R2 > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum. CONCLUSIONS: This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination.

A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298.

Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was vaccine efficacy against incident persistent anal infection with quadrivalent vaccine types or single detection at the final visit that were not present at baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week 52, persistent oral HPV infection. Results: A total of 575 participants were randomized. The Data and Safety Monitoring Board stopped the study early due to futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%) for prevention of persistent anal infection or single detection at the final visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%, 98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%, 74%) for 6-month persistent oral HPV infection or single detection at the final visit. Conclusions: These results do not support HPV vaccination of HIV-infected adults aged ≥27 years to prevent new anal HPV infections or to improve anal HSIL outcomes. However, our data suggest a role for prevention of oral HPV infections, but this finding should be confirmed in future studies. Clinical Trials Registration: NCT01461096.

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

BACKGROUND: Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. METHODS: In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. FINDINGS: Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. CONCLUSION: Our results indicate that a single dose of quadrivalent HPV vaccine is immunogenic and provides lasting protection against HPV 16 and 18 infections similar to the three- and two-dose vaccine schedules, although the study suffer from some limitations. Data on long term protection beyond 7 years against HPV infection and cervical precancerous lesions are needed before policy guidelines regarding a single dose can be formulated and implemented. Significant and long-lasting protective effect of a single dose can be a strong argument to introduce one dose of the HPV vaccine in many low income countries where the current standard of care for cervical cancer prevention is 'no intervention'.

Explanations for the high potency of HPV prophylactic vaccines.

HPV L1 virus-like particle (VLP) vaccines administered in a prime/boost series of three injections over six months have demonstrated remarkable prophylactic efficacy in clinical trials and effectiveness in national immunization programs with high rates of coverage. There is mounting evidence that the vaccines have similar efficacy and effectiveness even when administered in a single dose. The unexpected potency of one dose of these VLP vaccines may largely be attributed to structural features of the particles, which lead to the efficient generation of long-lived antigen-specific antibody-producing cells and unique features of the virus life cycle that make the HPV virions highly susceptible to antibody-mediated inhibition of infection.