Effectiveness of HPV vaccines against genital warts in women from Valencia, Spain

doi:10.1016/j.vaccine.2017.04.080

Vaccine

Volume 35, Issue 25, 5 June 2017, Pages 3342-3346

https://doi.org/10.1016/j.vaccine.2017.04.080 Get rights and content

Highlights

•
The quadrivalent and bivalent HPV vaccines include two high-risk genotypes.
•
The quadrivalent vaccine also includes HPV6 and 11, associated with genital warts.
•
We analysed effectiveness of both vaccines in preventing genital warts.
•
Three doses of the quadrivalent vaccine had an effectiveness > 77%.
•
The bivalent vaccine was not effective against genital warts in the same population.

Abstract

Objectives

To assess the effectiveness of the HPV vaccines in preventing genital warts in young women.

Design

Population-based study using health databases.

Setting

Valencian Community (Spain).

Participants

All girls and women aged 14–19 years who were registered in the Valencian Community between January 2009 and December 2014 (n = 279,787).

Main outcome measures

Incident cases of genital warts were defined as the first activation of diagnosis code ICD-9-CM 078.11 (Condyloma acuminatum) in primary care and outpatient clinics during the study period.

Results

There were 612 cases of genital warts. The overall incidence rate was 75.8/100,000 person-years (95% CrI 69.7–81.8). There was a decrease in genital warts when female candidates to be vaccinated with quadrivalent HPV vaccine reached the age of 18 (in 2012), compared to previous years. Incidence of genital warts in unvaccinated women and those who received the bivalent vaccine was higher than in girls and women who received the quadrivalent HPV vaccine. The effectiveness of a three-dose regimen of the quadrivalent HPV vaccine was 77% (95 CrI: 66–85%), whereas that of a single dose was 61% (95 CrI: 20–87%). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine.

Conclusions

Three doses of the quadrivalent HPV vaccine were effective against genital warts in our population. Moreover, with low vaccine coverage the incidence of genital warts decreased only in the vaccinated.

Introduction

Genital warts are a frequent sexually-transmitted disease (STD) [1]. It has been estimated that about 5–10% of the population will have at least one episode of genital warts during their lifetime [2], [3], [4]. The epidemiology of genital warts varies depending on age, gender, geographical area, and study methodology. A recent literature review has described an overall (females and males combined) annual incidence of genital warts (both new and recurrent) from 160 to 289/100,000 person-years [1]. Peak incidence occurs in women before 24 years of age and in men aged 25–29 years [1].

Genital warts have an important impact on the psychological, social and physical welfare of patients [5], significantly impairing their quality of life [6]. Furthermore, recurrences are frequent (around 20–30%) [7]. Over 90% of genital warts are related to HPV6/11 [8], [9].

In Europe there are three licensed vaccines containing recombinant HPV L1 capsid proteins. All three include the two most frequent high-risk HPV genotypes (HPV16/18, responsible for 70% of cervical cancer cases), and two also include the low-risk genotypes HPV6/11 [10].

In subjects aged 16 and over enrolled in clinical trials, the efficacy of the quadrivalent HPV vaccine in preventing genital warts associated with HPV6 and 11 was 100% (95% CI 92–100) in women after a mean follow-up of 3 years [11], and 89.4% (95% CI 65.5–97.9) in men after a median follow-up of 2.9 years [12]. In the long-term follow-up studies, no case of diseases associated with the four types of HPV covered by the vaccine occurred within 9–10 years after vaccination [11].

Post-authorization studies used different methodologies in geographical areas with different vaccination schedules [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. These studies demonstrated the significant, and rapid, impact of the quadrivalent HPV vaccination: the incidence of genital warts diminished in the vaccinated population [8], [23] and the disease was almost eradicated in vaccinated women under the age of 21 years, amongst whom the rate of vaccination coverage is high [14]. Significant herd immunity, protecting the unvaccinated population of both sexes, has been described when the vaccine coverage was over 50% [24]. In addition, the number of diagnoses of genital warts decreased in England two years after the onset of a vaccination programme with the AS04-adjuvanted HPV16/18 vaccine [25]. This vaccine does not contain the HPV genotypes 6 and 11.

In 2014 the Valencian Community in Spain had a population of 5 million, and its health system is organized into 24 health departments. All recommended vaccines are fully paid for by the National Health System; vaccines are bought every two years under a tender and any of the two available vaccines can be bought. The quadrivalent HPV vaccine was used only between 2008 and 2010 and was administered in a three-dose regimen to vaccinate girls born in 1994 and 1995, when they were 14 years old. Thereafter, the bivalent vaccine AS04-bHPV was used. The aim of the study was to assess the effectiveness of quadrivalent HPV and AS04-bHPV vaccines in preventing genital warts.

Section snippets

Methods

This is a population-based study using Valencia’s health databases. We assembled a cohort that included all the girls and women aged between 14 and 19 years registered in the Valencian Community between January 2009 and December 2014.

Results

The study cohort included 279,787 girls and women, who provided 809,864 person-years. The vaccination coverage of three doses of quadrivalent HPV vaccine in women born in 1994 and 1995 was 44.9%. In addition, 13.1% of the girls and women born between 1996 and 2000 were vaccinated with this vaccine. Vaccine coverage with AS04-adjuvanted bivalent HPV vaccine was 26.7% in girls and women born between 1996 and 2000, with a total of 31,326 vaccinated girls and women.

There were 612 cases of genital

Discussion

Valencia’s vaccination programme used the quadrivalent HPV vaccine for two years and then changed to the bivalent vaccine. This change allowed us to perform what we believe was the first analysis of the effectiveness of both HPV vaccines in preventing genital warts in the same population, and to assess the impact of this programme.

In Spain, the databases of the Valencia Region have proven to be very reliable in the surveillance of vaccine preventable diseases [26], as well as in the assessment

Conclusions

Contributorship

ENI is the principal investigator of the study, designed the study, and approved the final version.

PNI and JJV discussed the results and approved the final version.

MLL designed the statistical analysis plan, did the statistical analysis, discussed the results, had an input in the paper design, and approved the final manuscript.

JDD conceived the study, was involved in all parts of the study, and is the guarantor.

Competing interest declaration

ENI, MLL, and PNI have no conflict of interest.

JJV is speaker bureau of Sanofi Pasteur MSD (SPMSD).

JDD was speaker for SPMSD, was in Advisory boards (unrelated to HPV-vaccine) for SPMSD, and was sponsored for attending scientific meetings. His institution received grants from SPMSD.

Editorial assistance was provided by Content Ed Net, Madrid, Spain.

Funding

This study was done with FISABIO’s own resources. SPMSD sponsored the medical writer. SPMSD had no role in the design, collection, analysis, interpretation of the data and writing of the article, and had no access to the data. SPMSD did not intervene in the decision to submit the manuscript for publication.

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Prophylactic vaccination against human papillomavirus (HPV) is the cornerstone of the World Health Organization global strategy to accelerate the elimination of cervical cancer as a public health problem. At the end of 2007, the first two HPV vaccines were marketed in Spain. Therefore, 15 years have passed since the start of vaccination, included in the schedule of systematic immunizations for girls. Coinciding with this anniversary, this recommendation has been extended to boys. A vaccination that therefore achieves immunization equity, regardless of sex. The purpose of this work is to offer an update on vaccination against HPV in Spain after 5 years of the initial work previously published on the historical origins of the virus and the beginnings of this immunization, the second (after hepatitis B) for the prevention of cancer, and of the achievements and advances obtained.
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Se trata de un estudio observacional descriptivo retrospectivo realizado en la UITS de un Servicio de Dermatología entre enero de 2016 y junio de 2019, seleccionando posteriormente a los pacientes diagnosticados de condilomas acuminados.
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Genital warts are caused by the human papillomavirus (HPV), whose genotypes have traditionally been classified as low risk or high risk (oncogenic). The first 2 prophylactic vaccines included the most common genotypes at the time: HPV-6, HPV-11, HPV-16, and HPV-18. The aim of this study was to evaluate the prevalence of HPV types in our setting 10 years after the introduction of HPV vaccines.
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In total, 362 patients were diagnosed with genital warts during the study period, and 212 (58.6%) underwent genotyping. Thirty-two distinct HPV types were observed, the most common being HPV-6, HPV-11, HPV-16, and HPV-42. HPV DNA was detected in 93.9% of the samples analyzed, and there were 299 genotypes (mean, 1.5 per patient). Overall, 26.6% of patients had more than a single HPV genotype, while 24.1% had at least 1 high-risk type. No significant associations were found between the presence of high-risk HPV types and any of the study variables. At least 2 of the 4 HPV types targeted in the original vaccines were detected in 94.1% of lesions.
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In this updated systematic review of HPV vaccination effect by number of doses, we included 35 observational studies that evaluated outcomes of vaccine-type HPV infection, anogenital warts or cervical abnormalities. Among 29 studies that evaluated three doses, 28 found evidence of significant effectiveness [11–13,15–17,19–24,27,28,30,32–37,39–44]. Among 29 studies that evaluated two doses, 19 found significant effectiveness [12,13,15,17,19–22,27,28,30–33,35,38–41].
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Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009–2017
2022, Vaccine
Citation Excerpt :
The impact of HPV vaccination on GW incidence has been investigated in several studies around the world, reporting significant decreases of GW diagnoses in vaccinated girls and women [9,23]. Among them, very few have reported data on the population-level impact of single-cohort HPV vaccination programs [24,27] and none reported VE using individual-level data. Concretely, Brotons et al. [23] have recently showed a decline of 61% of GW incidence among women aged 16–19 years who were eligible for HPV vaccination in Catalonia.
To assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65.
Population-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID).
All subjects aged 14–65 years residing in the Valencia Region during 2009–2017 (n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine effectiveness (VE) estimations.
Incident cases of GW defined as the first activation of GW-related codes (ICD-9-CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) × 100 by a negative binomial Bayesian model.
There were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14–23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI 100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine.
A complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girls.

View all citing articles on Scopus

¹: ENI and MLL contributed equally to the conduct of the study and are co-first authors.

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Effectiveness of HPV vaccines against genital warts in women from Valencia, Spain

Highlights

Abstract

Objectives

Design

Setting

Participants

Main outcome measures

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Contributorship

Competing interest declaration

Funding

Vaccine

Enferm Infecc Microbiol Clin

Lancet Infect Dis

Clin Ther

Systematic review of the incidence and prevalence of genital warts

BMC Infect Dis

Genital warts and their treatment

Clin Infect Dis

Genital warts among 18- to 59-year-olds in the United States, national health and nutrition examination survey, 1999–2004

Sex Transm Dis

The burden of genital warts: a study of nearly 70,000 women from the general female population in the 4 Nordic countries

J Infect Dis

The quality of life of patients with genital warts: a qualitative study

BMC Pub Health

Impact of human papillomavirus-related genital diseases on quality of life and psychosocial wellbeing: results of an observational, health-related quality of life study in the UK

BMC Pub Health

2012 European guideline for the management of anogenital warts

J Eur Acad Dermatol Venereol

Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital warts: a systematic review

Adv Ther

Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males

N Engl J Med

Evaluating the early benefit of quadrivalent HPV vaccine on genital warts in Belgium: a cohort study

PLoS ONE

Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data

BMJ

Fall in genital warts diagnoses in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: analysis of routinely collected national hospital data

J Infect Dis

Impact of the human papillomavirus (HPV) vaccine on genital wart diagnoses at Auckland Sexual Health Services

N Z Med J