Introduction

The quadrivalent HPV (qHPV) vaccine clinical program included sexually active females regardless of baseline HPV status. Therefore, per-protocol efficacy analyses for each vaccine HPV type (HPV6/11/16/18) included participants infected by other vaccine or non-vaccine HPV types. The qHPV vaccine demonstrated consistently high clinical efficacy in females aged 16–45 years. The vaccine is prophylactic, without efficacy against disease caused by HPV types present before vaccination.

Methods

We summarize data from the randomized, placebo-controlled, double-blind, international FUTURE I (NCT00092521), II (NCT00092534), and III (NCT00090220) qHPV vaccine studies in females aged 16–26 (N=17,622; FUTURE I and II) and 24–45 years (N=3819; FUTURE III). HPV DNA positivity was a surrogate for current infection; anti-HPV seropositivity and HPV DNA negativity was a surrogate for past infection.

Results

Clinical trial data indicate that infection with all vaccine HPV types is rare: 0.1% of 3578 North American females were positive for all four qHPV vaccine types by serology and/or HPV DNA; none were infected with all 9-valent HPV vaccine types. Most prevalent HPV infections in females aged 16–25 years consist of only one or two high-risk HPV types (Barr, Am J Obstet Gynecol 2008). In FUTURE I and II participants infected with 1–3 vaccine HPV types, the qHPV vaccine protected against HPV-related cervical and external genital disease caused by the remaining HPV types (FUTURE II Study Group, J Infect Dis 2007). The qHPV vaccine also prevented cervical and external genital disease in females aged 16–26 years and persistent infection in females 27–45 years regardless of previous exposure to vaccine HPV types (Olsson, Human Vaccines 2009; Castellsague, Br J Cancer 2011).

Conclusions

HPV vaccination can protect against HPV infection and disease in adults previously infected with HPV. Vaccination should not be withheld from sexually active individuals with prior HPV exposure.

Introduction

The full benefit of human papillomavirus (HPV) vaccines may not be realized in real-world settings due to delays in immunization. At older ages, many women will have already been exposed to HPV rendering this prophylactic vaccine less effective.This study aimed to determine the extent to which age at the time of immunization influences the vaccine’s effectiveness (VE) against HPV-attributable high-grade cervical lesions (HGCL).

Methods

We conducted a matched case-control study of women in New Haven County, Connecticut, where there is population-based surveillance for HGCL and genotyping of HPV from cervical specimens. Cases were vaccine-eligible women with a HGCL attributable to HPV 16 or 18. Controls were women with normal Pap smear results, matched to cases by age, medical practice, and date of Pap smear. Participants were interviewed and records were reviewed for immunization history and potential confounders. Matched odds ratios (mOR) from conditional logistic regression were estimated by age at time of immunization (<18 years, >19 years). The VE was estimated as 1-mOR. Multivariable models were used to adjust for potential confounding. Consensus estimates of the adjusted VE were calculated using Bayesian Model Averaging (BMA).

Results

A total of 312 women (108 cases and 204 controls) were included. Cases and controls were similar in age, race/ethnicity, marital status, level of education, income, use of contraception, and history of sexually transmitted diseases (Table 1). The adjusted effectiveness of >1 dose of the vaccine was 43%. When the first dose was given at <18 years of age, the VE was 77% (Figure 1).

Conclusions

These data quantify the clinical effectiveness of HPV vaccine and use real-world data to highlight the fact that the vaccine’s protective effect is greater when given <18 years of age. These empirical estimates provide evidence that can be used to promote timely immunization for adolescents.

Introduction

Subsidized human papilloma virus (HPV) vaccination has been offered on-demand and as catch-up for girls aged 13-18 in Sweden since 2006 with a coverage of 55-60%. Since the first women in Sweden eligible for vaccination entered the cervical screening program in 1993, questions on how to evaluate colposcopic have arisen.

Evidence is inconsistent as to whether colposcopic features for the detection of HSIL are influenced by specific HPV genotypes and there are no previous studies to our knowledge evaluating colposcopy in vaccinated and unvaccinated women from the same birth cohort entering the organized cervical screening program. As colposcopic impression may be different due to a reduction in the prevalence of vaccine-types HPV 16/18, the aim of the study was to compare the colposcopic impression between the groups.

Methods

Women in the 1994 and 1995 birth cohorts who entered in the screening program at age 23 in one region of Sweden and had a positive screening result were identified and underwent colposcopy.

Colposcopic impression was evaluated according to the Swedescore. Colposcopic opinion was assessed as benign, low grade, high grade or invasive. Punch biospsies were taken and histopathologic findings were used as golden standard.

Results

In 2018, 59 women from the 1994 birth cohort attended colposcopy, of which 19 (32%) reported being vaccinated. There were a total of 22 HSILs identified in the 1994 cohort. In the vaccinated group 25% (2/8) of women with HSIL had a Swedescore of 8-10 (indicating HSIL); 40% (4/10) in the unvaccinated group. Colposcopic opinion was evaluated as high grade in 75% (6/8) of women with HSIL in the vaccinated group; 70% (7/10) in the unvaccinated group.

Conclusions

Preliminary results indicate that colposcopic examination including the Swedescore and colposcopic opinion may be useful tools also in the evaluation of vaccinated women entering the cervical screening program in Sweden.

Introduction

Three licensed HPV vaccines are approved for 2- or 3-dose schedules: 0, 6 months or 0, 1-2, 6 months. Alternative dosing schedules, particularly single dose and extended intervals between doses (>=12 months), are being considered to address vaccine shortages or operationalize flexibility.

Methods

We searched PUBMED/MEDLINE for publications reporting anti-HPV-16 and -18 ELISA data as geometric mean titers (GMT) following administration of one of the licensed HPV vaccines (2vHPV, 4vHPV, and 9vHPV) to females ages 9-26 years. GMT ratios and confidence intervals (CIs) comparing alternative to standard schedules were calculated using mixed effects meta-regression controlling for baseline HPV status and disaggregated by vaccine, subtype, time point, and age group (9-14 and 15-26 years). Non-inferiority was defined as the lower bound of the 95% CI for the GMT ratio being greater than 0.5.

Results

Our search returned 2,464 studies, of which 24 were included in data analyses. Comparing extended interval to standard schedules (Table 1), at one month post last dose and 36 months post first dose the 2vHPV vaccine showed non-inferiority for HPV-18 but not HPV-16. The 4vHPV vaccine showed non-inferiority for both subtypes at all time points, except for one month post last dose for HPV-16. The 9vHPV vaccine demonstrated non-inferiority for both subtypes at one month post last dose. For single dose (Table 2), data was only available for 2vHPV and 4vHPV, which did not meet criteria for non-inferiority for either subtype at all time points and age groups compared.

Conclusions

When evaluated against standard schedules, although robust immunogenicity was demonstrated across all multi-dose groups, non-inferiority of extended interval dosing was mixed across vaccines, subtypes, and time points. Single dose did not meet criteria for non-inferiority in any comparisons. Sparse data limited the number of possible comparisons, and further research is warranted.

Introduction

Data on immunological memory following reduced-dose human papillomavirus (HPV) vaccine schedules are limited. Immune memory cells such as memory B cells (Bmem) and T-follicular helper T cells (Tfh) are important for generation of long-term memory responses. We examined Bmem and Tfh 1-month following a booster dose of 2vHPV (Cervarix®, GSK) in girls who were previously unimmunised or received 1, 2 or 3 doses of 4vHPV (Gardasil®, Merck Inc.) 6 years earlier.

Methods

We conducted a cohort study in 200 Fijian girls (15-19 years old) previously unimmunised, or immunised with 1-3 doses of 4vHPV 6 years earlier. Blood was taken pre- and 28 days following the 2vHPV booster dose. To determine HPV vaccine type immune memory cells, we conjugated HPV16 or 18 pseudovirions with a fluorescently-labelled probe (Alexa Fluor® 488), and then measured the HPV-specific response by flow cytometry using the following markers for Bmem (CD19, CD27, CD38, IgM, IgG) and Tfh (CD4, CXCR5, CD278 and CD279) responses.

Results

Following a dose of 2vHPV, there were similar proportions of CD27⁺IgG⁺HPV16⁺/18⁺ populations in girls who were previously immunised with 1, 2 or 3 doses of 4vHPV 6 years earlier. All were higher than unimmunised girls, although this was not significant. A weak correlation was found between CD27⁺IgG⁺16/18⁺ and HPV16/18 neutralising antibodies when the data were pooled (r=0.22, p=0.03). Analyses for the comparison of other cell populations (CD27⁺IgM⁺16/18⁺; memory IgM B cells, CD27⁺CD38⁺; plasmablast, CD4⁺CXCR5⁺PD-1⁺ICOS-1⁺; Tfh) are ongoing.

Conclusions

Prior immunisation with 1, 2 or 3 doses of 4vHPV generated similar levels of CD27⁺IgG⁺16/18⁺ Bmem after a booster dose of 2vHPV, suggesting that 1 dose may efficiently prime immunological memory responses. Additional analyses of specific immune memory cell populations will provide a better understanding of the potential usefulness of single dose HPV schedules in the long-term.