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At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender‐neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female‐restricted vaccination is problematic. Extended catch‐up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender‐neutral vaccination, this group can be protected by offering concomitant catch‐up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long‐lasting durability of vaccination‐induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost‐effectiveness modelling suggests that high‐coverage HPV vaccination in multiple population segments will be resource‐saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer. [ABSTRACT FROM AUTHOR]

This review is based on the recent EUROGIN scientific session: "Assessing risk of cervical cancer in the post‐vaccination era," which addressed the demands of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesion (SIL) triage now that the prevalence of vaccine‐targeted oncogenic high‐risk (hr) human papillomaviruses (HPVs) is decreasing. Change in the prevalence distribution of oncogenic HPV types that follows national HPV vaccination programs is setting the stage for loss of positive predictive value of conventional but possibly also new triage modalities. Understanding the contribution of the latter, most notably hypermethylation of cellular and viral genes in a new setting where most oncogenic HPV types are no longer present, requires studies on their performance in vaccinated women with CIN/SIL that are associated with nonvaccine HPV types. Lessons learned from this research may highlight the potential of cervical cells for risk prediction of all women's cancers. [ABSTRACT FROM AUTHOR]

The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n  = 2,850; Sweden, 2002–2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women. [ABSTRACT FROM AUTHOR]

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life‐years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992–1994 birth‐cohorts (30,139 females) were invited to a community‐randomized HPV16/18‐vaccination trial. A total of 9,482 female trial participants received HPV16/18‐vaccination in 2007–2009 at age of 13–15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014–2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high‐risk HPV types were: 0.5% (53/1,000 follow‐up years, 104) and 25% (2,530/104) in the frequently screened Arm 1; 0.2% (23/104) and 24% (2,413/104) in the infrequently screened Arm 2; and 3.1% (304/104) and 23% (2,284/104) in the safety Arm 3. Corresponding prevalence of HSIL/ASC‐H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former. What's new? As the first generation of girls vaccinated against HPV reach adulthood, it's time to re‐evaluate screening recommendations. Reducing the frequency of screenings could save money without increasing cervical cancer incidence. Here, the authors collected baseline data on the safety of less frequent cervical cancer screenings. They conducted a randomized trial of Finnish women born in 1992‐1994 and vaccinated against HPV16/18, in which participants are screened either once or three times by age 28. At baseline and the first safety interim analyses they found no difference in the incidence of HSIL/CIN3 lesions between the two groups, suggesting that infrequent screening for HPV‐vaccinated women does not compromise safety. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccination is still not reaching many high-risk populations. HPV16/18 vaccines offer cross-protection against other types, for example, HPV45. Both direct vaccine efficacy and indirect herd protection contribute to vaccination effectiveness.Methods: We used a dynamic transmission model, calibrated to cervical screening data from Italy, to estimate vaccination effectiveness against HPV16 and HPV45 infection, assuming for HPV45 either 95% or lower cross-protection.Results: Basic reproductive number was smaller (2.1 vs 4.0) and hence vaccine effectiveness and herd protection stronger for HPV45 than for HPV16. The largest difference in the reduction of infection prevalence in women <35 years old was found at 70% coverage in girls-only vaccination programs (99% vs 83% for total protection for HPV45 and HPV16, respectively, mainly owing to stronger herd protection, ie, 37% vs 16%). In gender-neutral vaccination, the largest difference was at 40% coverage (herd protection, 54% vs 28% for HPV16 and HPV45, respectively). With ≥80% coverage, even 50% cross-protection would reduce HPV45 by ≥94%.Conclusions: The characteristics of individual high-risk HPV types strongly influence herd protection and determine the level of coverage and cross-protection required to reduce or eliminate the infection through HPV vaccination. HPV16 infection and related cancers are the most difficult to eliminate. [ABSTRACT FROM AUTHOR]

The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix™) has been shown to be well-tolerated and immunogenic in females aged 10 to 55 years, and up to 100% effective for the prevention of HPV-16/18 infection and associated precancerous cervical lesions in females aged 15 to 25 years. This study is the first to evaluate the immunogenicity and safety of the vaccine in males. Methods: Healthy males aged 10 to 18 years were randomized (2:1 ratio) to receive HPV-16/18 AS04-adjuvanted vaccine (n = 181) or hepatitis B virus (HBV) control vaccine (n = 89) at 0, 1, and 6 months, and were followed for 7 months. Results: All initially seronegative subjects in the HPV-16/18 group seroconverted for HPV-16 and 18 (ELISA) at month 2. At month 7, all subjects were seropositive, and the HPV-16 and -18 antibody levels were, respectively, four- and twofold higher than at month 2. The anti-HPV-16 and -18 antibody responses for males aged 10 to 18 years and 10 to 14 years, respectively, were higher than those reported for females aged 15 to 25 years and 10 to 14 years, respectively, in a previous study. The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were similar, except that pain and swelling at the injection site were more common in the HPV-16/18 group. However, vaccine-related symptoms did not affect compliance with the three-dose course, which was equally high (97%) in both groups. Conclusions: The HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well tolerated in boys aged 10 to 18 years. However, further data on the potential public health benefits of vaccination of boys are required before any recommendations can be made. [Copyright &y& Elsevier]

Disease trend studies based on birth cohort analysis and serological studies indicate that recent generations have a higher prevalence of oncogenic Human Papilloma Virus (HPV) types, and are likely to be at higher risk of cancer than previous generations. This implies that prevention strategies to protect young populations from HPV-associated cancers need to be strengthened, and hence organized implementation of vaccination and better screening programs are being considered. In this context, randomized large-scale policy evaluations will be instrumental in accelerating disease control and improve effective prevention programs. This report shares experiences from Nordic countries with examples of prevention strategies through vaccination and cervical screening. The same principles as set up for organized programs and new HPV technologies may apply for screening and vaccination as key tools to eliminate cervical cancer in the Nordic countries and globally. [ABSTRACT FROM AUTHOR]

Genital human papillomavirus (HPV) infection and HPV-associated cervical and other anogenital cancers are significant public health problems. HPV 16 and HPV 18 are responsible for approximately 70% of all invasive cervical cancers worldwide. The first prophylactic HPV virus-like particle (VLP) vaccine against HPV types 6/11/16/18 was licensed in 2006 for girls and women aged 9-26 years. The second prophylactic HPV vaccine against HPV types 16 and 18 has been licensed this year. These vaccines are almost 100% effective in preventing infection and high-grade precancer associated with the HPV types included in the vaccine. The vaccines are well tolerated, safe, and highly immunogenic when given in three doses within 6 months. Efficacy of the vaccine against external vulvar and HPV-related vaginal lesions is also high. Even though the vaccine is highly effective against high-grade cervical, vaginal, or vulvar precancers, this only applies to women unexposed to these HPV types and only to high-grade intraepithelial lesions caused by these HPV types. Therefore, it is important to understand that the population impact of the vaccines will be much lower than vaccinating naive populations. Implementing HPV vaccine is a great opportunity but also a great challenge. However, mandatory HPV vaccination may raise many questions, and more answers are needed. [ABSTRACT FROM AUTHOR]

Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1–2.0); B7 (1.5, 1.1–2.0); B15 (0.6, 0.4–0.8); DR2 (1.2, 1.1–1.4) and DR6 (0.6, 0.5–0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1–2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357–3189 HPV16/18 vaccine recipients, 3357–3189 other vaccine recipients, and 6714–9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether serum antibody response to the three versions of chlamydial heat shock protein 60 is associated with an increased risk for cervical cancer.Study Design: Women with cervical carcinoma were identified by linking the data files of three Nordic serum banks with cancer registries. Overall, 178 women with invasive cervical carcinoma were identified. For each case, the earliest prediagnostic serum sample was chosen, and three matched control subjects who were free of cancer at the time of the case diagnosis were selected randomly. Serum antibodies to the chlamydial heat shock protein 60 were measured by enzyme-linked immunosorbent assay and correlated with the risk of the subsequent development of cervical cancer.Results: Antibodies to chlamydial heat shock protein 60-1 were associated with cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds ratio, 2.4; 95% CI, 1.1-5.1). Antibodies to chlamydial heat shock protein 60-2 or chlamydial heat shock protein 60-3 were not associated with cervical cancer risk.Conclusions: The finding that chlamydial heat shock protein 60-1 antibodies are associated with an increased cervical cancer risk suggests that persistent Chlamydia trachomatis infection may contribute to cervical neoplasia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Infection with oncogenic human papillomaviruses (HPVs) is the most important cause of cervical cancer worldwide. After infection there is a long latency period of at least 10 to 15 years during which cervical cancer develops in a small proportion of originally infected women. Up to 50% of these women have at diagnosis antibodies to the HPV oncoproteins E6 and E7, which are rarely found among healthy women. Our purpose was to evaluate whether antibodies to HPV16 and HPV18 E6 and E7 proteins are useful for early diagnosis of cervical cancer by measuring the antibody response in women in whom cervical cancer later developed. STUDY DESIGN: A joint serum bank of 550,000 Swedish, Norwegian, and Finnish women was followed up for 0.5 to 20 years, after which 178 invasive cervical carcinoma (ICC) cases, 150 of whom had squamous cell carcinoma (SCC), and 527 controls were identified. Antibodies to HPV16 and HPV18 E6 and E7 proteins were determined by tag enzyme-linked immunoassays. RESULTS HPV16/18 E6 and E7 antibodies were detected infrequently (7.0%) in women in whom SCC later developed and yielded a moderately increased estimate of associated relative risk (odds ratio 2.7, 95% CI 1.1-6.4). Sensitivity of the combined antibody tests for the detection of occult. SCC varied between 6% and 14% but was not related to time lag between serum sampling and cancer diagnosis. CONCLUSION: HPV16/18 E6 and E7 antibody responses are not sensitive markers of occult cervical cancer. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) play the major role in cervical carcinogenesis. The authors reevaluated the role of herpes simplex virus type 2 (HSV-2) in this multistage process by conducting a longitudinal, nested case-control study using 1974-1993 data and comparing the results with those from a meta-analysis of studies. A Nordic cohort of 550,000 women was followed up for an average of 5 years, after which 178 cervical carcinoma cases and 527 controls were identified. HSV-2; HPV-16, HPV-18, and HPV-33; and Chlamydia trachomatis antibodies were determined at baseline by HSV-2 glycoprotein gG-2 and HPV virus-like-particle enzyme immunoassays and by using the microimmunofluorescence method. The relative risk of cervical carcinoma was calculated by conditional logistic regression. Longitudinal studies on HSV-2 and cervical neoplasia were identified through MEDLINE (National Library of Medicine, Bethesda, Maryland), and weighted mean relative risks were calculated. Smoking (relative risk = 1.6, 95% confidence interval (CI): 1.1, 2.3) and HPV-16/HPV-18/HPV-33 (relative risk = 2.9, 95% CI: 1.9, 4.3) were both associated with cervical carcinoma. The smoking- and HPV-16/HPV-18/HPV-33--adjusted relative risks for HSV-2 were 1.0 (95% CI: 0.6, 1.7) and 0.7 (95% CI: 0.3, 1.6), respectively, for HPV seropositives. In the meta-analysis, the relative risk for HSV-2 was 0.9 (95% CI: 0.6, 1.3). In both sets of data, HSV-2 did not play a role in cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Reports on a study of the association between exposure to different Chlamydia trachomatis serotypes and subsequent development of cervical squamous cell carcinoma (SCC) in women. Design; Setting; Subjects; Results; Conclusion that Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC while others also increase risk.

Abstract: Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405, 000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0. 023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV. [ABSTRACT FROM AUTHOR]

Defines the role of human papillomavirus (HPV) infection in cervical carcinogenesis, with invasive cancer as an endpoint. HPV infection and other risk factors for invasive cervical cancer; Link between cervical cancer risk and the number of lifetime sexual partners; Ecologic studies comparing areas with high and low risk of cervical cancer for HPV prevalence.

The article focuses on human papillomavirus (HPV) vaccines that are needed to be included in national programs. It refers to 9% of cancers in women that are caused by highrisk HPV (hrHPV) types. It highlights virus-like particles self-assembling from papillomavirus L1 proteins included in licensed, prophylactic HPV vaccines.

Comments on the promise shown by vaccination against human papillomaviruses. The long course to discovery of the causes of cervical cancer; The rapid breakthrough in finding a vaccine for prevention; Description of a study in this journal on a phase 2 trial of a combination vaccine of HPV16 and HPV18; Need for long-term passive follow-up to prove that the HPV vaccination ultimately protects against invasive cervical cancer; Probability that this will become the first licensed vaccine against a common sexually transmitted infection; Several questions which have yet to be answered about how the vaccine will be used.

Abstract: We review studies of the implementation of human papillomavirus (HPV) vaccination programmes in developed and developing countries. The review spans the period from establishment of long-term vaccine efficacy follow-up studies, operational research on issues of vaccine preparedness, and relevant predictive modelling studies during the pre-licensure phase to plans of phase IV effectiveness trials, forms of epidemiological surveillance, and further operational research in the post-licensure phase. Much of the research is already ongoing. Depending on the results of the planned immuno bridging studies among HIV-negative and HIV-positive women, further phase III and/or phase IV trials may be warranted. [Copyright &y& Elsevier]

Introduction: Human papillomavirus-vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated.Study Design: This was an intervention study.Setting/participants: Study participants were women aged 25-45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018.Intervention: Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination.Main Outcome Measures: Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019.Results: Among 3,646 participants, 2,748 (range by country=50%-96%) accepted vaccination, and 2,151 (range=30%-93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%-59%) and the need for more information on human papillomavirus vaccines (range=1%-72%). No safety issues were experienced by vaccinated women.Conclusions: Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings.Trial Registration: EudraCT Number 2014-003177-42. [ABSTRACT FROM AUTHOR]

Abstract: Background: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. Methods: A total of 552, 16–23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years’ follow-up. A subset of 241 subjects (n =114 in the quadrivalent HPV vaccine group and n =127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. Results: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. Discussion: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting. [Copyright &y& Elsevier]

Abstract: Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were ∼12- to 26-fold higher than those observed in baseline-naïve women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported. [Copyright &y& Elsevier]

Summary: Background: A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). Methods: 277 young women (mean age 20·2 years [SD 1·7]) were randomly assigned to quadrivalent HPV (20 μg type 6, 40 μg type 11, 40 μg type 16, and 20 μg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20·0 years [1·7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. Findings: Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71–97, p&#60;0·0001) in those assigned vaccine compared with those assigned placebo. Interpretation: A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types. Published online April 7, 2005 DOI 10.1016/S1470-2045(05)70101-7 [Copyright &y& Elsevier]