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Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18–related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18–related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18–related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.

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Supplementary Table 1 from Smoking and Passive Smoking in Cervical Cancer Risk: Pooled Analysis of Couples from the IARC Multicentric Case–Control Studies

Supplementary Table 2 from Smoking and Passive Smoking in Cervical Cancer Risk: Pooled Analysis of Couples from the IARC Multicentric Case–Control Studies

Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions.Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 24 to 34, and 35 to 45 years, respectively. A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, among women ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively.Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58.Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1. Cancer Epidemiol Biomarkers Prev; 23(10); 1997–2008. ©2014 AACR.

HPV DNA Detection

Supplementary Table 1 - Study design and comparison of protocols 013, 015 and 019. Supplementary Table 2 - Selected Characteristics at Baseline by Histologic Diagnosis.

Background: The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS).Methods: A pooled analysis of 1,919 couples enrolled in one of seven case–control studies involving cervical carcinoma in situ (CIS) or ICC was investigated. Information on smoking and sexual behavior was collected from interviews. Specimens were taken from the cervix and penis for human papillomavirus (HPV) DNA testing. Three PS risk models were constructed with all couples, couples with monogamous women, and couples with lifetime nonsmoking monogamous women. For the third model, the analysis considered potential misclassification of smoking status and was restricted to the risk period for which the woman was exposed to both HPV, a necessary cause of ICC, and PS. Multivariable unconditional logistic regression was used to estimate associations between CIS or ICC and PS.Results: An increased risk was found among couples with both ever smoking men and women (OR = 2.26; 95% CI: 1.40–3.64). No statistically increased risk of CIS was found with PS in the models analyzed. Similar significant increased risks of ICC with PS was found among all couples (OR = 1.57; 95% CI: 1.15–2.15) and couples with monogamous women (OR = 1.55; 95% CI: 1.07–2.23) but not among lifetime nonsmoking monogamous women married to ever smoking men.Conclusion: PS could not be detected as an independent risk factor of ICC in the absence of active smoking.Impact: The combined effects of exposure to active and PS suggest its potential adverse role in cervical carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(7); 1379–90. ©2011 AACR.

There are few pathologic or molecular studies of penile precancerous lesions, and the majority refers to lesions associated with invasive carcinomas. Penile Intraepithelial Neoplasia (PeIN) is classified in two morphologically and distinctive molecular groups, non-HPV and HPV-related with special subtypes. The primary purpose of this international series was to classify PeIN morphologically, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

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. publishedVersion

Background Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. Methods A total of 4072 healthy men ages 18–70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. Results MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. Conclusions This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC.

Introduction Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. Methods A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. Results Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. Conclusion These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.

Background To ensure the highest quality of human papillomavirus (HPV) testing in primary cervical cancer screening, novel HPV assays must be evaluated in accordance with the international guidelines. Furthermore, HPV assay with genotyping capabilities are becoming increasingly important in triage of HPV positive women in primary HPV screening. Here we evaluate a full genotyping HPV assay intended for primary screening. Methods The CLART® HPV4S (CLART4S) assay is a newly developed full-genotyping assay detecting 14 oncogenic (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) and two non-oncogenic HPV genotypes (6, 11). It was evaluated using SurePath and ThinPrep screening samples collected from the Danish and Swedish cervical cancer screening programs, respectively. For calculation of sensitivity, 81 SurePath and 80 ThinPrep samples with confirmed ≥CIN2 were assessed. For clinical specificity analysis, 1184 SurePath and 1169 ThinPrep samples from women with Results In SurePath samples, the sensitivity of CLART4S was 0.90 (MGP-PCR =0.93) and the specificity was 0.91 (MGP-PCR = 0.91); In ThinPrep samples the sensitivity of CLART4S was 0.98 (MGP-PCR = 1.00) and specificity was 0.94 (MGP-PCR =0.87). The CLART4S was shown to be non-inferior to that of MGP-PCR for both sensitivity (p = 0.002; p = 0.01) and specificity (p = 0.01; p = 0.00) in SurePath and ThinPrep samples, respectively. Intra-laboratory reproducibility and inter-laboratory agreement was met for both media types. The individual genotype concordance between CLART4S and MGP-PCR was good agreement for almost all 14 HPV genotypes in both media types. Conclusions The CLART4S assay was proved non-inferior to the comparator assay MGP-PCR for both sensitivity and specificity using SurePath and ThinPrep cervical cancer screening samples from the Danish and Swedish screening programs, respectively. This is the first study to demonstrate clinical validation of a full-genotyping HPV assay conducted in parallel on both SurePath and ThinPrep collected samples.

This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising.

The discovery and validation of human papillomavirus (HPV) as cause of cervical cancer is one of the most successful stories in medicine. However, the road to reaching this point is paved with fascinating vignettes of early clashes between scientific disciplines. In their own merit they could not complete the complex puzzle of cervical cancer’s multifactorial etiology. To complicate matters, incoherent molecular epidemiologic discoveries in the late 1980s fanned the flames of skepticism. Fortunately, concerted effort by the scientific community in the 1990s brought coherence to the picture and results from vaccination trials allayed any lingering concerns. Today, this is part of history. The rich translational science that evolved from these cooperative lines of inquiry gave the world two new prevention fronts: HPV vaccination and molecular HPV testing. Deployed in tandem, these two strategies will eventually eliminate cervical cancer.

Extensive multiple-age cohort human papillomavirus (HPV) vaccination has proved to be highly effective. We aimed to determine the 8-year population impact of a female single-age cohort HPV vaccination programme on the incidence of anogenital warts (AGW). In 2008, Catalonia initiated a school-based quadrivalent HPV vaccination programme targeting 11-year-old girls, achieving coverage over 80%. Data on diagnoses of AGW and genital herpes were obtained from a population-based database of electronic health records covering 74% of the population. The annual incidence rates from 2009 to 2016 were calculated, stratified by age and sex using Joinpoint regression to estimate trends and annual percentage changes (APC). Among women aged 16–19 years, the AGW incidence decreased by 61% from 2012 to 2016 (APC −19.4%; 95% CI: −30.0 to −7.3). In contrast, the incidence of genital herpes in same-aged women increased throughout the study period (APC 11.1%; 95% CI: 7.2–15.2). Among men aged 20–22 years, the increasing incidence of AGW shifted to a downward trend in 2013 (APC 2009–2013: 17.0%; 95% CI: 8.2–26.5; and APC 2013–2016: −4.5%; 95% CI: −14.6 to 6.9). A similar pattern was observed among men aged 23–25 years (APC 2009–2014: 16.0%; 95% CI: 12.0–20.2; and APC 2014–2016: −6.0%; 95% CI: −18.4 to 8.3). In contrast to AGW, among men aged 20–25 years, the incidence of genital herpes increased over this period. Our study strongly suggests that a single-cohort HPV vaccination strategy with high vaccine uptake not only provides direct benefit in the vaccinated cohorts but also extends protection through a herd effect to unvaccinated men.

Simulation models are commonly used to address important health policy issues that cannot be explored through experimental studies. These models are especially useful to determine a set of strategies that result in a good value for money (cost-effectiveness). Several mathematical models simulating the natural history of HPV and related diseases, especially cervical cancer, have been developed to calculate a relative effectiveness and cost-effectiveness of HPV vaccination and cervical cancer screening interventions. Virtually all cost-effectiveness analyses identify HPV vaccination programmes for preadolescent girls to be cost-effective, even for relatively low vaccination coverage rates. Routine vaccination of preadolescent girls is the primary target population for HPV vaccination as it shows to provide the greatest health impact. Cost-effectiveness analyses assessing other vaccine target groups are less conclusive. Adding additional age-cohorts would accelerate health benefits in some years, although cost-effectiveness becomes less favourable as age at vaccination increases. Including men in HPV vaccination programmes may be a less efficient strategy if done at the expense of female vaccination coverage for reducing the burden of HPV in the population. However, as the HPV vaccine price decreases, the cost-effectiveness of universal vaccination improves, becoming equally as efficient as female-only vaccination. Vaccine price is a decisive factor in the cost-effectiveness analyses. The lower the price, the greater the likelihood that vaccination groups other than the primary target would be considered cost-effective.

The Human Papillomavirus (HPV) Prevention and Control Board convened a meeting in Bucharest, Romania (May 2018), to discuss the role of healthcare providers (HCPs) in prevention programs, with a focus on HPV vaccination and cervical cancer screening. International and local experts discussed the role that HCPs can play to increase the uptake of HPV vaccine and screening. Experts recommended: 1) increasing HCP norms of getting vaccinated; 2) training providers to make effective recommendations; 3) making culturally appropriate materials available, in local languages; and 4) centralizing and coordinating education and information material, to direct both HCPs and the general public to the best material available.

Mycotoxins are toxic metabolites produced by certain fungi growing on agricultural commodities in the field and/or during storage. Mycotoxin occurrence on commodities susceptible to mold infestation is largely unavoidable; environmental factors such as temperature, humidity, and extent of rainfall during the preharvest, harvest, and postharvest periods influence mycotoxin production. The mycotoxins most commonly found in naturally contaminated foods include ergot, aflatoxins, trichothecenes, fumonisin, ochratoxins, zearalenone, and patulin. Epidemics of ergotism have been described in recorded history, being most numerous between the 9th and 18th centuries. Two types of disease have been noted: gangrenous and convulsive ergotism. Aflatoxin impairs the cellular and humor immune system, making animals more susceptible to bacterial, viral, fungal, and parasitic disease Since animals consuming aflatoxin often succomb to infectious disease, aflatoxin as the initiating factor often is overlooked. Most of the information on disease outcomes related to aflatoxin exposure has been derived from animal models.

HPV screening and vaccination are complementary preventive options often implemented as separate and non-coordinated public health programs. The HPVFASTER protocols aim to address this disconnect by combining both strategies with the ultimate purpose of accelerating the reduction of cervical cancer incidence and mortality and making the programs both costeffective and sustainable. Results from two phase III trials comparing HPV vaccination against placebo among adult women (aged up to 45 years and 55 years for 4vHPV and 2vHPV vaccines, respectively)1,2 showing high protection against HPV type specific infections and persistent infections and the excellent and consistent results of the HPVscreening trials3-5 provide the basis for the HPV-FASTER proposal. The recognition of indications to vaccinate adult women in Europe6-8 and the US9 which do not include an upper age limit, favor the exploration of combined protocols of screening and vaccination and broadening the vaccine indications in developed and developing countries.

Human papillomavirus virus-like particles (HPV VLPs) have distinctive immunogenic properties that generate a durable antibody response, producing high-quality neutralizing antibodies. By vaccination, i.e., intramuscular injection of these HPV VLPs, the viral survival strategy of avoiding exposure to the systemic immune system is completely overruled, and large amounts of vaccine-induced systemic antibodies are generated. These systemic circulating antibodies are easily transuded to the genital mucosa and are detectable in female genital secretions. It is well accepted that these antibodies interact with the virions presented by an infected partner and inhibit infection. However, much less attention has been paid to the role of anti-HPV vaccine-induced antibodies in an HPV-infected individual where infectious virions are encountered by neutralizing antibodies in mucosal secretions. There is a clear need to further investigate and document this role. Indeed, if HPV vaccination of HPV-infected women has an effect on HPV transmission, auto-inoculation, and relapse after treatment, this may influence how we model, assess, and implement HPV vaccination programmes. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Cervical cancer remains within the three most common cancer in women worldwide and is still the commonest female cancer in 41 of 184 countries. Within Latin America, cervical ranks as the most common cancer among women in Bolivia and Peru and the second most frequent in Brazil, Colombia, Ecuador, Mexico, Paraguay, The Guyanas, Surinam and Venezuela. Due to its relatively early age at onset, it ranks among the three most frequent cancers in women aged below 45 years in 82% of all countries in the world irrespective of their screening practices. DOI: http://dx.doi.org/10.21149/spm.v58i2.7777

To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59).A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods.During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs.Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs.CLINICALTRIALS.GOV,: NCT00092521 and NCT00092534.

Summary Background There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. Methods Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. Findings We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7–79·1), two doses was 76·0% (62·0–85·3), and one dose was 85·7% (70·7–93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0–63·0), two doses was 37·7% (12·4–55·9), and one dose was 36·6% (–5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2–87·5) and 82·6% (42·3–96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0–87·0; CVT data only), but not those receiving it at one month (10·1%, −42·0 to 43·3), was similar to the three-dose group. Interpretation 4 years after vaccination of women aged 15–25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. Funding US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Mediante el uso de sistemas de expresión celulares o microbianos se ha sintetizado partículas similares a virus a partir de proteínas L1 auto-ensambladas. Las vacunas profilácticas basadas en dichas partículas previenen en forma eficaz las infecciones y lesiones causadas por los tipos de VPH incluidos en sus preparados. Ensayos clínicos con tres prototipos de vacunas (una con VPH 16, otra con VPH 16 / 18 y otra con VPH 6/11/16/18) han demostrado que son seguras, inmunogénicas y altamente eficaces para prevenir NIC 2/3, precursores inmediatos del carcinoma de cuello uterino. La implementación de programas de vacunación con cobertura aceptable, tendría el potencial de reducir sustancialmente la morbilidad y mortalidad por cáncer de cérvix. Este artículo enfoca los resultados de los ensayos clínicos de las vacunas.

Analysis of the cervical cancer screening activity in the National Health System of Catalonia has identified a cytological coverage at 3 years of 40.8%, an interval of 2.4 years between Pap smears and a loss to follow-up of 50% at 3 years in women aged 25-65 years old. The introduction of human papillomavirus testing in the management of women with cytological results of atypical squamous cell of undetermined significance and as an adjunct to cytology in women with a history of inadequate screening has facilitated the management and detection of women at risk of developing cervical intraepithelial neoplasia grade 2 or worse (CIN2 + ). Human papillomavirus testing has demonstrated high sensitivity and specificity at 3 years in the detection of CIN2 + and was substantially superior to cytology. Furthermore, it had good inter-laboratory reproducibility and was easy to perform in routine situations. The use of uniform protocols and the extensive availability of software tools have allowed comprehensive and reliable assessment across Catalonia. The protocol has been complemented with educational interventions for healthcare professionals and regular monitoring of all activities. We conclude that the introduction of organized screening programs and human papillomavirus testing among women older than 30 years can greatly enhance efforts for the secondary prevention of CC in Catalonia.