Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

Background

Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2.

Methods

We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively.

Results

Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines.

Conclusion

Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys.     

Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study

Background

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.

Methods & Findings

We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies.

Conclusions

We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.     

Human Papillomavirus Types Distribution in Organised Cervical Cancer Screening in France

Background

Knowledge of prevalence rates and distribution of human papillomavirus (HPV) genotypes prior high HPV vaccine coverage is necessary to assess its expected impact on HPV ecology and on cervical lesions and cancers.

Methods

Residual specimens of cervical cytology (N = 6,538) were obtained from 16 sites participating in organised cervical cancer screening pilot programs throughout France, anonymised and tested for HPV DNA using the PapilloCheck® genotyping test. Samples were stratified according to age of women and cytological grades.

Results

The age-standardised prevalence rates of HPV 16 and/or 18 (with or without other high-risk types) was 47.2% (95% Confidence Interval, CI: 42.4–52.1) in high-grade squamous intraepithelial lesions (HSILs), 20.2% in low-grade SIL (95% CI: 16.7–23.7) and 3.9% (95% CI: 2.8–5.1) in normal cytology. Overall HR HPV were detected in 13.7% (95%I CI: 11.7–15.6) of normal cytology. In women below 30 years of age, 64% of HSILs were associated with HPV16 and/or 18. In our study population, HPV16 was the most commonly detected type in all cervical grades with prevalence rates ranking from 3.0% in normal cytology to 50.9% in HSILs. HPV16 was also detected in 54% (27/50) of invasive cervical cancers including 5 adenocarcinomas.

Conclusion

HPV16 was strongly associated with cervical precancer and cancer. The high prevalence rates of HPV16/18 infection among women below 30 years of age with HSILs suggests that the impact of vaccination would be primarily observed among young women.     

Anal HPV infection in HIV-positive men who have sex with men from China

Background

Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM), especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China.

Methods

A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping.

Results

A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%). HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3%) were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%), HPV16 (13.0%), HPV52 (8.5%) and HPV11 (7.6%). Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001), which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection.

Conclusions

A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV.     

Human Papillomavirus Infection: Knowledge, Attitudes, and Behaviors among Lesbian, Gay Men, and Bisexual in Italy

Background

This cross-sectional study assess knowledge, attitudes, and behavior towards the human papillomavirus (HPV) and the vaccination among a random sample of 1000 lesbian, gay men, and bisexual women and men.

Methods

A face-to-face interview sought information about: socio-demographic characteristics, knowledge about HPV infection, perception of risk towards HPV infection and/or cervical, anal, and oropharyngeal cancers, perception of the benefits of a vaccination to prevent cervical, anal, and oropharyngeal cancers, sexual behaviors, health-promoting behaviors, and willingness to receive the HPV vaccine.

Results

Only 60.6% had heard about the HPV infection and this knowledge was significantly higher in female, in those being a member of a homosexual association, in those having had the first sexual experience at a younger age, in those having received information about the HPV infection from physicians, and in those having no need of information about HPV infection. A higher perceived risk of contracting HPV infection has been observed in those younger, lesbian and gay men, who have heard of HPV infection and knew the risk factors and its related diseases, who have received information about HPV infection from physicians, and who need information about HPV infection. Only 1.7% have undergone HPV immunization and 73.3% professed intent to obtain it in the future. The significant predictors of the willingness to receive this vaccine were belief that the vaccination is useful, perception to be at higher risk of contracting HPV infection, and perception to be at higher risk of developing cervical, anal, and oropharyngeal cancers.

Conclusions

Information and interventions are strongly needed in order to overcome the lack of knowledge about HPV infection and its vaccination. Inclusion of boys in the national vaccination program and initiate a catch-up program for men who have sex with men up to 26 years may reduce their burden of HPV-related disease.     

Efficacy of vaccination against HPV infections to prevent cervical cancer in France: present assessment and pathways to improve vaccination policies

Background

Seventy percent of sexually active individuals will be infected with Human Papillomavirus (HPV) during their lifetime. These infections are incriminated for almost all cervical cancers. In France, 3,068 new cases of cervical cancer and 1,067 deaths from cervical cancer occurred in 2005. Two vaccines against HPV infections are currently available and vaccination policies aim to decrease the incidence of HPV infections and of cervical cancers. In France, vaccine coverage has been reported to be low.

Methods

We developed a dynamic model for the heterosexual transmission of Human Papillomavirus types 16 and 18, which are covered by available vaccines. A deterministic model was used with stratification on gender, age and sexual behavior. Immunity obtained from vaccination was taken into account. The model was calibrated using French data of cervical cancer incidence.

Results

In view of current vaccine coverage and screening, we expected a 32% and 83% reduction in the incidence of cervical cancers due to HPV 16/18, after 20 years and 50 years of vaccine introduction respectively. Vaccine coverage and screening rates were assumed to be constant. However, increasing vaccine coverage in women or vaccinating girls before 14 showed a better impact on cervical cancer incidence. On the other hand, performing vaccination in men improves the effect on cervical cancer incidence only moderately, compared to strategies in females only.

Conclusion

While current vaccination policies may significantly decrease cervical cancer incidence, other supplementary strategies in females could be considered in order to improve vaccination efficacy.     

Rapid Emergence of Free-Riding Behavior in New Pediatric Immunization Programs

Background

Mathematical models have formalized how free-rider effects can threaten the stability of high vaccine coverage levels under established voluntary vaccination programs. However, little research has addressed the question of when free-riding begins to develop when a new vaccine is first introduced in a population.

Methodology/Principal Findings

Here, we combine a game theoretical model of vaccinating behavior with an age-structured compartmental model to analyze rational vaccinating behavior in the first years of a universal immunization program, where a new vaccine is free to all children of a specified age. The model captures how successive birth cohorts face different epidemiological landscapes that have been shaped by the vaccinating decisions of previous birth cohorts, resulting in a strategic interaction between individuals in different birth cohorts. The model predicts a Nash equilibrium coverage level of for the first few birth cohorts under the new program. However, free-riding behavior emerges very quickly, with the Nash equilibrium vaccine coverage dropping significantly within 2-5 years after program initiation. Subsequently, a rich set of coupled dynamics between infection prevalence and vaccinating behaviors is possible, ranging from relatively stable (but reduced) coverage in later birth cohorts to wide fluctuations in vaccine coverage from one birth cohort to the next. Individual tolerance for vaccine risk also starts out at relatively high levels before dropping significantly within a few years.

Conclusions/Significance

These results suggest that even relatively new immunization programs can be vulnerable to drops in vaccine coverage caused by vaccine scares and exacerbated by herd immunity effects, necessitating vigilance from the start.     

Genital Human Papillomavirus Infection among Women in Bangladesh: Findings from a Population-Based Survey

Background

There has been no population-based study on human papillomavirus (HPV) prevalence or its genotypes in Bangladesh; a country eligible for GAVI funding for HPV vaccine.

Methods

We used baseline survey data of a prospective cohort study that was conducted in one urban and one rural area of Bangladesh. A total of 997 urban and 905 rural married women, aged 13 to 64 years, were enrolled in the baseline during July-December, 2011. Information was collected on socio-demographic characteristics and potential risk factors for HPV infection followed by gynecological examination and collection of endocervical samples using the cervical cytobrush (Digene cervical sampler). HPV DNA testing was done by Polymerase Chain Reaction (PCR) using a consensus primer set.

Results

Prevalence of any HPV infection was 7.7% with no significant difference between urban and rural women. Most common high-risk genotypes were HPV16, HPV66, HPV18, HPV45, HPV31 and HPV53. Urban women working as housemaids or garment workers were at higher risk of any HPV infection (OR = 2.15, 95% CI: 1.13–4.11) compared to housewives. Rural women whose husband lived overseas were almost two times more likely to have any HPV infection (OR = 1.93; 95% CI 1.05–3.55) compared to women whose husbands lived with them.

Conclusion

The prevalence of HPV infection among Bangladeshi women is similar to other regions of Asia. However, type-specific patterns are different. The study findings will inform the formulation of HPV vaccination policies in Bangladesh, monitoring the impact of vaccination programmes, and the identification of target populations for screening.     

HPV Infections among MSM in Shenzhen,China

Background

An increasing incidence of anal cancer among men, especially men who have sex with men (MSM) suggests a need to better understand anal human papillomavirus (HPV) infection among this group.

Methods

A cross-sectional study was conducted among MSM in Shenzhen, China. Blood was collected for HIV serological testing and syphilis serological screening, and anal swabs were collected for HPV genotyping. Difference of HPV prevalence between HIV seropositive and HIV seronegative MSM was assessed by chi-square test. Factors associated with anal canal HPV infection were assessed by univariate and multivariate logistic regression.

Results

A total of 408 MSM were recruited. HIV and HPV prevalence were 6.9% and 36.4%, respectively. HPV was detected in the anal canal in 71.4% of the HIV-positive MSM and in 33.8% of the HIV-negative MSM (P<0.001). Oncogenic types were seen more often in anal specimens of HIV-positive MSM than in specimens of HIV-negative MSM (P = 0.001). The HPV genotypes detected most frequently were HPV06 (8.2%), HPV16 (7.2%), HPV11 (6.4%), HPV18 (4.7%), HPV58 (4.7%), and HPV52 (4.2%).

Conclusions

In this study, HIV positive MSM had a higher burden of HPV infection, especially oncogenic HPV infection. HPV types 52 and 58 were as popular as those types designed for the currently available vaccine (HPV6, 11, 16, 18).     

Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China

Background

In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China.

Methods

HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes.

Results

Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04).

Conclusions

High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology.     

Prevalence and risk factors of Human Papillomavirus (HPV) infection in southern Chinese women - a population-based study

Background

Persistent high-risk type Human papillomavirus (HPV) infection is recognized as a necessary cause of cervical cancer. This study aimed to compare the HPV prevalence and risk factors between women residing in Hong Kong (HK) and Guangzhou (GZ) region of China.

Methodology/Principal Findings

A total of 1,570 and 1,369 women were recruited from HK and GZ, respectively. The cytology samples were collected and tested for HPV infection. The overall and type-specific HPV prevalence and the potential risk factors for acquisition of HPV infection were studied. Women with normal cytology in the GZ cohort had significantly higher HPV prevalence (10%) than those in the HK cohort (6.2%, p<0.001). The patterns of the age-specific HPV prevalence were also different between the two cohorts. In the HK cohort, women at the age of 20–29 years old had the highest prevalence and a second peak was observed in the age of ≥60 years old. In the GZ cohort, the highest HPV prevalence was also observed in 20–29 years old but declined as the age increased and a second peak was not seen. HPV16 and HPV52 were the most common high-risk types found in the HK and GZ cohorts, respectively. Age was the most consistently observed independent risk factor for HPV infection in the HK, while the number of sexual partners had association in the GZ cohort.

Conclusions/Significance

Our study provides the current status and the epidemiological characteristics of HPV prevalence in Southern Chinese women. The results strongly suggested that population education and the effective cervical cancer screening would be vital in the prevention of cervical cancer.     

Sexual Behaviour and HPV Infections in 18 to 29 Year Old Women in the Pre-Vaccine Era in the Netherlands

Background

Infection with Human Papillomavirus (HPV) is a necessary event in the multi-step process of cervical carcinogenesis. Little is known about the natural history of HPV infection among unscreened young adults. As prophylactic vaccines are being developed to prevent specifically HPV 16 and 18 infections, shifts in prevalence in the post vaccine era may be expected. This study provides a unique opportunity to gather baseline data before changes by nationwide vaccination occur.

Methods and Principal Findings

This cross-sectional study is part of a large prospective epidemiologic study performed among 2065 unscreened women aged 18 to 29 years. Women returned a self-collected cervico-vaginal specimen and filled out a questionnaire. All HPV DNA-positive samples (by SPF₁₀ DEIA) were genotyped using the INNO-LiPA HPV genotyping assay. HPV point prevalence in this sample was 19%. Low and high risk HPV prevalence was 9.1% and 11.8%, respectively. A single HPV-type was detected in 14.9% of all women, while multiple types were found in 4.1%. HPV-types 16 (2.8%) and 18 (1.4%) were found concomitantly in only 3 women (0.1%). There was an increase in HPV prevalence till 22 years. Multivariate analysis showed that number of lifetime sexual partners was the most powerful predictor of HPV positivity, followed by type of relationship, frequency of sexual contact, age, and number of sexual partners over the past 6 months.

Conclusions and Significance

This study shows that factors independently associated with HPV prevalence are mainly related to sexual behaviour. Combination of these results with the relative low prevalence of HPV 16 and/or 18 may be promising for expanding the future target group for catch up vaccination. Furthermore, these results provide a basis for research on possible future shifts in HPV genotype prevalence, and enable a better estimate of the effect of HPV 16-18 vaccination on cervical cancer incidence.     

Human Papillomavirus Infection in a Male Population Attending a Sexually Transmitted Infection Service

Objective

Human Papillomavirus (HPV) infection in men may produce cancer and other major disorders. Men play an important role in the transmission of the virus and act as a reservoir. The aim of this study was to determine the HPV-genotypes and their prevalence in a group of men attending a Sexually Transmitted Infection service.

Patients and Samples

Between July 2002 and June 2011, 1392 balanopreputial, 435 urethral, 123 anal, and 67 condyloma lesions from 1551 men with a mean age of 35.8±11.3 years old (range: 17–87) were collected for HPV-DNA testing.

Methods

A fragment of the L1-gene and a fragment of the E6/E7-genes were amplified by PCR. Positive samples were typed by hybridization.

Results

The HPV genome was detected in 36.9% (486/1318) balanopreputial and in 24.9% (101/405) urethral (p<0.0001) swabs from 38.1% (538) of 1469 men. Co-infections were present in 5.4% (80/1469) of cases. HPV was found in 43.9% (373/850) of men younger than 35 vs. 31.7% (187/589) of men aged >35. HPV was found in 59.4% (104) of 165 men with lesions (macroscopic or positive peniscopy), and in 22.8% (61/267) without clinical alterations. HPV was also detected in 71.4% (40/56) men with condylomata and in 58.7% (64/109) of men with positive peniscopy.

Conclusions

HPV prevalence in men was high and decreased with age. HPV was found more frequently in balanopreputial than in urethral swabs. There was a low rate of co-infections. Low-risk HPV vaccine genotypes were the most recurrent especially in younger. Although HPV has been associated with clinical alterations, it was also found in men without any clinical presentation. Inclusion of men in the national HPV vaccination program may reduce their burden of HPV-related disease and reduce transmission of the virus to non-vaccinated women.     

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

Background

Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.

Methods

To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.

Results

Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.

Conclusions

The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.     

Human Papillomavirus Genotype Distribution in Czech Women and Men with Diseases Etiologically Linked to HPV

Background

The HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.

Methods

We analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing.

Results

Thirty different HPV genotypes were detected in our study, HPV 16 being the most prevalent type both in precancerous lesions (45%) and squamous cell carcinomas (59%). In benign lesions, HPV 6 (72%) was the most common type. Altogether, 61% of carcinoma samples and 43% of precancerous lesion samples contained HPV 16 and/or 18. The presence of HPV types related to the vaccinal ones (HPV 31, 45, 33, 52, 58) were detected in 16% of carcinoma samples and 18% of precancerous lesion samples. HPV 16 and/or 18 were present in 76% of cervical cancer samples, 33% of CIN1, 43% CIN2 and 71% of CIN3 samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.

Conclusions

The prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic.     

Multivalent Human Papillomavirus L1 DNA Vaccination Utilizing Electroporation

Objectives

Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV) L1 and L2 DNA vaccination.

Methods

Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11−88 of 8 different HPV types (11−88×8) or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.

Results

Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2) vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type.

Discussion

Multivalent vaccination via in vivo electroporation requires spatial separation of individual type L1 DNA vaccines.     

Epidemiology of Anal HPV Infection in High-Risk Men Attending a Sexually Transmitted Infection Clinic in Puerto Rico

Purpose

Recent studies in Puerto Rico have reported an increasing incidence of anal cancer in Puerto Rican men. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among men attending an STI clinic in Puerto Rico.

Methods

We conducted a cross-sectional study among 205 men 18 years and older. A comprehensive survey was administered that included a demographic and a behavioral assessment. Separate logistic regression models were performed to determine factors associated with any, high-risk (HR), and multiple anal HPV infection.

Results

The mean age of the study sample was 38.0±13.5 years. The most common HR types were 58, 51 and 31. Overall, HR anal HPV infection was found in 53.5% of the participants. Multiple HPV types in the anal canal were found in 47.6% of the sample. A third (29.8%) of participants reported being men who had sex with men (MSM). MSM had a significantly higher prevalence of any, HR and multiple HPV infection (p-value<0.05). Separate multivariate logistic regression analyses showed that being MSM was associated with any (OR = 4.5; [95%CI: 1.9–10.7]), HR (OR = 3.4; [95%CI: 1.1–10.3) and multiple anal HPV infection (OR = 3.6; [95%CI: 1.5–9.1). HIV was marginally associated with multiple anal HPV infection in multivariate analysis (OR = 3.3; 95%CI = 1.0–11.0).

Conclusions

Anal HPV is common among sexually active men attending this STI clinic, with higher likelihood of anal HPV infection among MSM.     

Dynamics of Japanese Encephalitis Virus Transmission among Pigs in Northwest Bangladesh and the Potential Impact of Pig Vaccination

Background

Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs.

Methodology/Principal Findings

We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs.

Conclusions/Significance

The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease.     

Human Papillomavirus Type-Specific Prevalence in the Cervical Cancer Screening Population of Czech Women

Background

Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.

Objectives

The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.

Methods

Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).

Results

Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.

Conclusions

Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.