Impact of HPV vaccination : health gains in the Italian female population

Abstract Background Human papillomavirus (HPV) is the leading cause of cervical cancer and other malignant and benign neoplastic lesions. HPV vaccination has three potential goals: to prevent transmission, infection, and disease. At present, there are no available data about health consequences of HPV immunization in Italy. The aim of this study is to evaluate the effect of current HPV vaccination strategy in Italy. Methods A multistate morbidity-mortality model was developed to estimate the infection process in a theoretical cohort of Italian women. The Markov process considered nine health states (health, anogenital warts, grade 1 and grade 2/3 cervical intraepithelial neoplasia, cervical cancer, anal cancer, death due to cervical cancer, anal cancer and other causes), and 26 transition probabilities for each age group. The model was informed with the available data in national and international literature. Effectiveness of immunization was assumed considering a literature review pertaining to models and vaccination coverage rates observed in Italy. Life expectancy (ex), Quality-Adjusted Life Years (QALYs), Disability-Adjusted Life Years (DALYs), and attributable risk (AR) were estimated for no intervention (cervical cancer screening) and vaccination strategies scenarios. Results The model showed that in a cohort of 100,000 Italian women the e0 is equal to 83.1 years. With current HPV vaccination strategy the e0 achieves 83.2 (+0.1) years. When HPV-related diseases are considered altogether, the QALYs increase from 82.7 to 82.9 (+0.2 QALYs) with no intervention and vaccination strategies respectively. DALYs decrease by 0.6 due to vaccination. Finally, AR is equal to 93 and 265 cases per 100,000 women in population and not vaccinated, respectively. Conclusion When mortality due to cervical cancer is considered, HPV vaccination seems to have a low impact on health unit gains in the Italian female population. Conversely, when several HPV-related and cancer morbidity conditions are included, the effect of vaccination becomes quite remarkable

Economic burden of vulvar and vaginal intraepithelial neoplasia: retrospective cost study at a German dysplasia centre

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus is responsible for a variety of diseases including grade 2 and 3 vulvar and vaginal intraepithelial neoplasia. The aim of this study was to assess parts of the burden of the last diseases including treatment costs. The direct medical resource use and cost of surgery associated with neoplasia and related diagnostic procedures (statutory health insurance perspective) were estimated, as were the indirect costs (productivity losses) associated with surgical treatment and related gynaecology visits for diagnostic purposes.</p> <p>Methods</p> <p>Data from 1991-2008 were retrospectively collected from patient records of the outpatient unit of the Gynaecological Dysplasia Clinic, Heinrich Heine University, Dusseldorf, Germany. Two subgroups of patients were analysed descriptively: women undergoing one surgical procedure related to a diagnosis of vulvar and/or vaginal intraepithelial neoplasia, and women undergoing two or more surgical procedures. Target measures were per-capita medical resource consumption, direct medical cost and indirect cost.</p> <p>Results</p> <p>Of the 94 women analysed, 52 underwent one surgical intervention and 42 two or more interventions (mean of 3.0 interventions during the total period of analysis). Patients undergoing one surgical intervention accrued €881 in direct costs and €682 in indirect costs; patients undergoing more than one intervention accrued €2,605 in direct costs and €2,432 in indirect costs.</p> <p>Conclusions</p> <p>The economic burden on German statutory health insurance funds and society induced by surgical interventions and related diagnostic procedures for grade 2/3 vulvar and vaginal neoplasia should not be underrated. The cost burden is one part of the overall burden attributable to human papillomavirus infections.</p

Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions

BACKGROUND: The new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases. METHODS: This cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact. RESULTS: At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR?=?3.51 (95% CI, 1.29-9.56), PFe-adjusted?=?0.72 (95% CI, 0.22-0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions. CONCLUSION: The greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions

Human papillomavirus prevalence in women attending routine cervical screening in South Wales, UK: a cross-sectional study

In this cross-sectional population-based study we determine human papillomavirus (HPV) prevalence in South Wales to provide comprehensive baseline data for future assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. Liquid-based cytology samples from women attending routine cervical screening were collected (n=10 000: mean age 38 years, 93% cytology negative, and 64.8% from the 50% least deprived LSOA according to social deprivation score (SDS)). High-Risk (HR) and Low-Risk HPV screening was performed using HPV PCR-EIA with genotyping of HR positives and data correlated with age, SDS and cytology. Overall HPV prevalence was 13.5% (9.3% age standardised) and the most frequent HR types were HPV 16, 31, 18 and 58. In HR HPV-positive cases 42.4% had a single HR type and they were predominant in women with severe cytological abnormalities. Here, 66% of all HR HPV cases were in women aged 30 years of age or less and SDS had no significant effect on HPV status. HPV prevalence increased significantly with degree of dyskarosis from 7% in cytology negative samples to 80% in samples with severe cytological abnormalities (P-value <0.0001). Overall, 46% of HR HPV cases were positive for the two HR types targeted by the prophylactic vaccines (HPV 16 and HPV 18). The data presented represents the largest type-specific investigation of HPV prevalence in an unselected UK population

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada

Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies

Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact

Background Estimation of pre-immunisation prevalence of HPV and distribution of HPV types is fundamental to understanding the subsequent impact of HPV vaccination. We describe the type specific prevalence of HPV in females aged 20--21 in Scotland who attended or defaulted from cervical screening using three specimen types; from attenders liquid based cytology and from defaulters urine or self-taken swabs. Methods Residual liquid based cytology samples (n = 2148), collected from women aged 20--21 attending for their first smear were genotyped for HPV. A sample (n = 709) from women who had defaulted from screening was also made available for HPV testing through the use of postal testing kits (either urine samples (n = 378) or self-taken swabs (n = 331)). Estimates of prevalence weighted by deprivation, and for the postal testing kit, also by reminder status and specimen type were calculated for each HPV type. The distribution of HPV types were compared between specimen types and the occurrence of multiple high-risk infections examined. The influence of demographic factors on high-risk HPV positivity and multiple infections was examined via logistic regression. Results The prevalence of any HPV in young women aged 20--21 was 32.2% for urine, 39.5% for self-taken swab, and 49.4% for LBC specimens. Infection with vaccine specific types (HPV 16, 18) or those associated with cross-protection (HPV 31, 33, 45, 51) was common. Individuals were more likely to test positive for high-risk HPV if they resided in an area of high deprivation or in a rural area. The overall distribution of HPV types did not vary between defaulters and attenders. Multiple infections occurred in 48.1% of high-risk HPV positive individuals. Excluding vaccine types the most common pairing was HPV 56 and 66. Conclusions Understanding of the pre-immunisation prevalence of HPV in young women puts Scotland in a prime position to assess the early effect of vaccination as the first highly vaccinated cohorts of individuals enter the screening programme. Differences in results with different specimen types must be taken into account when monitoring the impact of vaccination programmes

Skin Cancer:Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches

Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection