Welcome to the IPVC 2023 Conference Program Scheduling
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PREVALENCE AND FACTORS ASSOCIATED WITH CONCORDANT ANOGENITAL HUMAN PAPILLOMAVIRUS (HPV) INFECTION FOR 9-VALENT (9V) HPV VACCINE TYPES IN MALES
Abstract
Introduction
Previous studies in males did not quantify global prevalence and risk factors of concordant HPV infection (ie, same-type infection) across multiple anogenital sites.
Methods
Baseline data from males aged 16-27 participating in a global 4-valent HPV vaccine trial (NCT00090285) were assessed for prevalent HPV infection at penile/scrotal and perineal/perianal sites (heterosexual men [HM] and men who have sex with men [MSM]) and at intra-anal sites (MSM). Categories were HPV-negative for all 9vHPV vaccine types (6/11/16/18/31/33/45/52/58) across all anogenital sites, non-concordant infection (infection at one site), or concordant infection (at two or three sites). Factors associated with concordant 9vHPV infection at ≥2 sites were assessed using an age-adjusted logistic regression model.
Results
Included were 3364 HM and 595 MSM. Among HM with prevalent 9vHPV infection, 329/455 (72.31%) had non-concordant infection at one anogenital site and 126/455 (27.69%) had concordant infection at two sites. Among MSM with prevalent 9vHPV infection (excluding intra-anal sites), 118/171 (69.01%) had non-concordant infection and 53/171 (31.00%) had concordant infection at two sites; concordant infection at any two or three sites (including intra-anal sites) was observed in 92/229 (40.17%) and 49/229 (21.40%) MSM, respectively. HPV6 and HPV16 were most likely to occur at multiple anogenital sites in HM and MSM. Factors associated with statistically significant increased odds of concordant infection (p<0.05) were geographic region (both HM and MSM; higher in Africa, Europe and Latin America than in North America), higher number of lifetime partners (both HM and MSM), and younger age at first intercourse (HM only). Decreased odds of concordant infection were associated with circumcision in both HM and MSM.
Conclusions
A high proportion of HM and MSM with prevalent infection at baseline had concordant 9vHPV infection, suggesting a risk of HPV-associated cancer at multiple anogenital sites.
LONG-TERM EFFICACY, IMMUNOGENICITY, AND SAFETY OF THE QUADRIVALENT AND 9-VALENT HPV VACCINES: AN OVERVIEW OF CLINICAL TRIAL LONG-TERM FOLLOW-UP STUDIES
Abstract
Introduction
Given the lifetime risk of HPV infection, prophylactic HPV vaccine clinical programs must demonstrate durable protection against infection and disease. Pivotal baseline clinical trials of the quadrivalent (qHPV) and 9-valent (9vHPV) vaccines were extended to assess long-term effectiveness against infection and disease up to 14 years (y).
Methods
Six long-term follow-up (LTFU) extension studies were designed to evaluate long-term effectiveness of the qHPV (NCT00092534, NCT00090220, NCT00090285, NCT00092547) and 9vHPV (NCT00943722, NCT02653118) vaccines in females (aged 9-45y) and males (aged 9-26y), with follow-up periods of 10-14y. Endpoint evaluation was carried out in a rigorous fashion throughout the studies. Tissue samples collected because of lesions suspicious for HPV-related disease were analyzed. Pathology panel adjudication was performed on all tissue specimens, and HPV typing was conducted to determine endpoint attribution. In some studies, participants randomized to placebo in qHPV vaccine trials who received catch-up qHPV vaccination at the end of the base study were followed during LTFU to evaluate effects of delayed vaccination at an older age.
Results
Across all studies, the qHPV and 9vHPV vaccine demonstrated durable effectiveness; no cases of high-grade cervical, vulvar, vaginal, and anal dysplasia or condyloma related to vaccine-targeted HPV types were observed during LTFU. Vaccine effectiveness was also observed in the catch-up qHPV vaccination groups. The LTFU studies included participants vaccinated at various ages (9-45y), of both genders, of various sexual orientations (heterosexual men and men having sex with men), and various countries across five continents, which supports the generalizability of the results.
Conclusions
Over 10-14y, qHPV and 9vHPV vaccines provided sustained protection with no breakthrough disease related to HPV vaccine types across studies in males vaccinated at ages 9-26y and females vaccinated at ages 9-45y. Catch-up vaccination was effective, suggesting that vaccination of adults not previously vaccinated may be beneficial.
MULTICENTRIC COHORT STUDY TO COMPARE LONG-TERM EFFICACY OF A SINGLE-DOSE OF 4-HPV VACCINE COMPARED TO TWO- & THREE-DOSE IN 10-18 YR OLD FEMALES IN INDIA
Abstract
Introduction
In a multi-centric Indian cohort study, unmarried girls aged 10-18 years received three doses, two doses or a single dose of the quadrivalent vaccine. We present 10-year immune responses, and 12-year follow-up findings on the efficacy of single-dose compared to other doses in preventing persistent HPV infection and high grade cervical precancers for the vaccinated and age-matched unvaccinated cohorts.
Methods
Around 17,000 vaccinated (evenly distributed across different dose groups) and 1,450 unvaccinated women are being followed up yearly. Serology samples were obtained at months 0, 7, 12, 18, 24, 36, 48, 60 and 120 after first dose from a convenient sample of vaccinated participants and at one timepoint from unvaccinated women. Cervical samples are collected initially at 18-months after marriage and yearly thereafter for at least four consecutive samples. E7-PCR multiplex genotyping is performed on the samples to detect 19 high or probable high-risk and two low-risk types. Married participants are screened for cervical cancer starting at 25 years with Hybrid Capture-II HPV test
Results
Ten years after vaccination, the antibody levels were at least two times higher in single dose recipients compared to those following natural infection. Based on evaluation of 2454 single-dose recipients in the year 2021, the vaccine efficacy against persistent HP16/18 infections was estimated to be 94% for the single-dose, which was similar to that of two-dose (95%) and three-dose (91%) recipients. No HPV16/18-related CIN2/3 detected in vaccinated women. Updated results based on evaluation of 2,730 single-dose recipients evaluable for persistent infection will be presented along with updated outcomes of cervical screening.
Conclusions
Systematic and rigorous evaluation of infection endpoints in the IARC-India study has established the robust protection offered by a single dose against persistent infection. The long-term protection is well-supported by immunogenicity data. Early data from screening outcomes is also encouraging.
HPV VACCINATION IN WOMEN WITH CERVICAL INTRAEPITHELIAL NEOPLASIA UNDERGOING EXCISIONAL TREATMENT: INSIGHTS INTO UNSOLVED QUESTIONS
Abstract
Introduction
Several questions regarding the role of vaccination in women treated for high-grade cervical intraepithelial lesion (HSIL) have not been clarified. One of the main queries is whether the time at which the vaccine is administered (before or after treatment) influences the protection against post-treatment HSIL. A second unsolved question is whether the vaccine has any effect in women with persistent HPV after treatment. We aimed to address these questions in a series of 398 women undergoing excisional treatment from July 2016 to December 2019
Methods
Vaccination was funded and offered to all women undergoing treatment. Post-treatment follow-up controls were scheduled every six months with a Pap smear, HPV testing, and a colposcopy
Results
306 women (76.9%) accepted HPV vaccination (vaccinated group): 113 (36.9%) received the first dose before excision and 193 (63.1%) after the procedure. 92 women (23.1%) refused the vaccine (non-vaccinated group). Women vaccinated before treatment showed a lower rate of post-treatment HSIL compared with non-vaccinated women (0.9% vs. 6.5%; p=0.047). Among women with persistent HPV infection after treatment, those who had received the vaccine showed a lower prevalence of post-treatment HSIL than non-vaccinated women (2.6% vs. 10.5%; p=0.043).
Conclusions
In conclusion, this study shows that HPV vaccination before treatment reduces the prevalence of post-treatment HSIL and suggests that vaccination might even benefit women with persistent HPV after treatment.
LONG-TERM EFFECTIVENESS OF THE 9-VALENT HUMAN PAPILLOMAVIRUS (9VHPV) VACCINE IN SCANDINAVIAN COUNTRIES
Abstract
Introduction
A long-term follow-up (LTFU) extension (NCT02653118) of the 9-valent human papillomavirus (9vHPV) vaccine efficacy study in women aged 16–26 years (y) (NCT00543543) was initiated to assess effectiveness and immunogenicity up to 14y. We report an interim analysis conducted at 8y post-vaccination for effectiveness and 9y for immunogenicity.
Methods
Participants from Denmark, Norway, and Sweden, who received 9vHPV vaccine during base study and consented, continued into LTFU. National health registries were used to assess those screened and diagnosed with cervical (pre)cancers. Cervical tissue from biopsy and definitive therapy exams were retrieved from clinical biobanks for adjudication of pathology diagnosis and tested for HPV DNA by PCR. To assess effectiveness, observed incidence of HPV16/18/31/33/45/52/58-related cervical intraepithelial neoplasia-2 (CIN2), CIN3, adenocarcinoma in situ, or cervical cancer was compared with estimated incidence in an unvaccinated cohort (similar age/risk). A control chart method was used to detect signals of vaccine effectiveness <90%. Blood was collected at 9y from a subset of participants to assess antibody persistence by competitive Luminex immunoassay. Primary analyses were conducted in the per-protocol effectiveness (PPE) and per-protocol immunogenicity populations.
Results
Of 2223 participants who received ≥1 dose of 9vHPV vaccine at start of base study, 2029 continued into LTFU. Analyses were conducted based on median effectiveness follow-up post-Dose 1 of 6.8y (maximum 10.0y) among participants included in PPE analyses (n=1799). No new cases of HPV16/18/31/33/45/52/58-related CIN2 or worse were observed during LTFU among 1448 PPE participants (4084.2 person-years). Analyses indicated no waning of vaccine effectiveness over ≥6y post Dose 1. There were indications of continued effectiveness through 8y post Dose 1. Immunogenicity analyses (n=150) showed that anti-HPV antibodies persisted through 9y post-vaccination. Effectiveness data ≥9y are not available.
Conclusions
The 9vHPV vaccine provides continued protection through ≥6y post-vaccination with a trend toward continued effectiveness for up to 8y, and persistent anti-HPV immunogenicity through 9y.
EFFECTIVENESS OF THE QUADRIVALENT HUMAN PAPILLOMAVIRUS VACCINE IN CHINESE WOMEN: A 13-YEAR LONG-TERM FOLLOW-UP OF A PHASE 3, DOUBLE-BLIND, RANDOMIZED CONTROL TRIAL
Abstract
Introduction
A randomized clinical trial (NCT00834106, V501-041) in Chinese women aged 20-45 years beginning in 2009 demonstrated the safety and efficacy of quadrivalent HPV (qHPV) vaccine during 78-month follow-up since Dose 1. A 13-year long-term follow-up (LTFU) study of V501-041 participants was conducted to evaluate the long-term effectiveness against cervical intraepithelial neoplasia (CIN).
Methods
During LTFU, the participants initially receiving the qHPV vaccine in V501-041 study constituted the early vaccination group (EVG). Those who initially received the placebo but were vaccinated from 2018 to 2020 were regarded as the catch-up vaccination group (CVG), while the control group (CG) comprised those remaining unvaccinated. A cytology-based cervical cancer screening was conducted. The endpoint was defined as histopathological-confirmed CIN2+ tested PCR-positive for HPV6/11/16/18. Effectiveness was computed by incidence. Incidence was compared between EVG and CG in the per-protocol (PP) population, and between EVG and CVG in the modified intention-to-treat (mITT) population.
Results
1100 subjects in V501-041, among which 978 were followed in LTFU, were included with a median follow-up of 152.2 months (interquartile range (IQR: 150.8-154.9) from Dose 1 to the last follow-up of LTFU study. During V501-041 study and LTFU, the incidence per 10 000 person-years of HPV-6/11/16/18-related CIN2+ was numerically higher in the CG (N=273; 3.4 (95% CI: 0.1-18.8)) than in the EVG (N=493; 0 (0.0-6.6)), indicating 100% (≤ -999, 100) risk reduction between two groups. For the CVG, no cases of HPV6/11/16/18-related CIN2+ were detected from vaccination to the last follow-up of the LTFU (N=155) (0.0 per 10 000 person-years (0·0–81.2)), while the incidence before vaccination was 22.2 per 10 000 person-years (4.6-64.9). These results represent observed long-term effectiveness through 13 years.
Conclusions
Reporting the longest follow-up for qHPV vaccine effectiveness in Chinese women, this study demonstrated continued protection against cervical precancers related to HPV6/11/16/18 through 13 years post-vaccination.
SINGLE DOSE OF NONAVALENT PROPHYLACTIC HPV VACCINE INDUCES STABLE HPV16 AND HPV18 ANTIBODY RESPONSES UP TO 24 MONTHS AMONG 9-11 YEAR-OLD GIRLS AND BOYS
Abstract
Introduction
Emerging data suggest that a single dose of the bivalent or quadrivalent HPV vaccine generates antibody responses and efficacies similar to 2-dose schedules in children. No similar data are yet available for the nonavalent vaccine (9vHPV). Such data may inform policy considerations around usage of a single dose of 9vHPV to reduce costs of vaccination worldwide.
Methods
This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial to determine the stability of HPV type-specific antibody responses up to 24 months after a single dose of 9vHPV in 201 healthy 9–11-year-old girls and boys. Subjects received a single dose of the 9vHPV at baseline, a delayed 2nd dose at month 24, and an optional 3rd dose at month 30. Blood samples were collected at baseline and at 6, 12, 18, 24, and 30 months after the prime dose. Primary outcomes were serum geometric mean concentrations (GMC) of HPV-16 and HPV-18 IgG antibodies.
Results
Demographics are shown in Table 1. GMCs of HPV16 and HPV18 antibodies are shown in Table 2. Table 3 shows high GMC at 6 months that declined between months 6 to 12, and stabilized between months 12, 18, and 24 (meeting the pre-specified hypotheses of non-inferior responses). The GMC were stable (or slightly higher) among 87.7% participants between months 12 and 24; among the remaining participants none showed consistent declines declines between both 18- vs. 12- and 24- vs. 18-months timepoint comparisons. Almost all participants (97%/96%) had significantly boosted responses for HPV16/HPV18 after the 3rd dose. One participant (0.5%) did not seroconvert after the single dose.
Conclusions
A single dose of 9vHPV induced persistent and stable antibody responses up to 24 months in the majority of participants, and a delayed dose at 24-months induces robust anamnestic responses. Declines and irregularities in antibody levels merit further study.
RISK OF PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA GRADE 2 BY HPV VACCINATION STATUS
Abstract
Introduction
Risk stratification of women with CIN2 is crucial as many countries have implemented active surveillance for CIN2 due to high regression rates. However, we are lacking variables that enable identification of women with higher risk of progression to CIN3+. As HPV-vaccinated women have lower risk of cervical cancer, HPV-vaccinated women with CIN2 may have lower risk of progression. Hence, we investigated whether HPV-vaccinated women undergoing active surveillance for CIN2 are less likely to progress to CIN3+ during surveillance compared to unvaccinated women.
Methods
Using nationwide registries, we conducted a population-based cohort study on all women aged 18-40 undergoing active surveillance for CIN2 during 2007-2020 in Denmark. The primary outcome was CIN3+ during the active surveillance period of 28 months. We calculated risk ratios (RR) using modified Poisson regression to evaluate the association between vaccination status and risk of CIN3+.
Results
A total of 9,203 women underwent active surveillance for CIN2 of whom 3,876 (42.1%) had received the HPV vaccine. Median age at CIN2 diagnosis was 26 (IQR 23-30), with vaccinated women being slightly younger than those unvaccinated. Overall, HPV vaccination was not associated with a lower risk of progression to CIN3+ compared to no vaccination (RR 0.98 (95% CI 0.93-1.04)). Stratified by age at vaccination, women vaccinated before age 15 (RR 0.67 (95% CI 0.58-0.77)) and between age 15 and 17 (RR 0.83 (95% CI 0.72-0.95)) had a lower risk of progression to CIN3+ compared to no vaccination. Adjusted RRs with age, index cytology, and socioeconomic status will be presented.
Conclusions
Our preliminary results suggest that HPV vaccination at a young age may be associated with a lower risk of progression of CIN2 in 28 months. There is potential for HPV vaccination status to be used for risk stratification of women with CIN2.
THE EFFECT OF TWO-DOSE AND THREE-DOSE VACCINATION WITH THE BIVALENT VACCINE ON TYPE-SPECIFIC HUMAN PAPILLOMAVIRUS VIRAL LOAD IN YOUNG WOMEN.
Abstract
Introduction
Persisting human papillomavirus (HPV) infections increase cervical cancer risk and are associated with increased viral load. In 2009, the Netherlands introduced a bivalent vaccine against highly oncogenic HPV16 and 18. Three-dose vaccination was provided to young women and changed to two doses in 2014, due to comparable effectiveness. Three-dose vaccination was especially effective against HPV16 and 18 infections and showed cross-protectivity against HPV31, 33, 35 and 45 infections. Here, we examined the effect of two-dose and three-dose vaccination on the viral load of type-specific HPV in clearing and persistent infections in young women.
Methods
Self-collected vaginal swabs from three-dose vaccinated and unvaccinated women participating in the HPV Among Vaccinated And Non-vaccinated Adolescents (HAVANA) study, or two-dose vaccinated and unvaccinated women participating in the HAVANA-2 study, were used. Total DNA isolation and HPV genotyping was performed with the Magna-Pure-96 and SPF10-DEIA-LiPA25 platforms, respectively. HPV viral load was measured using type-specific qPCR assays and corrected for cellular content with a β-actin qPCR assay.
Results
In the HAVANA study, HPV16, 18 and 31 viral loads in clearing infections were significantly reduced in three-dose vaccinated women compared to unvaccinated women (p=0.0020, p=0.00016 and p=0.00067, respectively), while type-specific viral load in persistent HPV infections remained similar. Two-dose vaccinated and unvaccinated HAVANA-2 women had overall low infection numbers, thereby hampering subsequent viral load analyses. Infection with HPV16 and 18 were completely absent in two-dose vaccinated women. Despite low infection numbers, pooled HPV31/33/35/45 viral loads in two-dose vaccinated women showed a lower trend compared to unvaccinated women
Conclusions
Two-dose and three-dose vaccination reduces the viral load of vaccine and cross-protective HPV types. Vaccination may counteract HPV persistency by reducing the viral load of vaccine types and several cross-protective types at infection onset.