A Review of the Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: 10 Years of Clinical Experience in Canada.

Publicly funded administration of the quadrivalent HPV (qHPV) vaccine in school-aged girls was implemented for all Canadian provinces and territories between 2007 and 2009. However, the impact of female qHPV vaccination in Canada has yet to be evaluated. This systematic literature review of studies published between September 1, 2006 and September 1, 2016 looked at real-world evidence related to the effects of qHPV vaccination on prevalence of HPV infection and disease in Canada over the past decade. PubMed was searched for studies published between September 1, 2006 and September 1, 2016. Studies were eligible if one or more of the following outcomes were assessed in individuals receiving the qHPV vaccine though public immunization programs: HPV infection, anogenital warts (AGW), HPV-associated lesions of the anogenital tract. A "pre-public vaccination program" or "unvaccinated" reference group was required. Key HPV conference abstracts were also reviewed. We identified seven eligible studies representing five Canadian provinces. Results reported indicated that the prevalence of HPV types 6, 11, 16, and 18 was lower in qHPV-vaccinated than unvaccinated individuals (1.5% vs. 11.0%, respectively), whereas non-vaccine-covered genotypes were comparable across vaccination status. Risk of AGW incidence decreased by up to 45% in vaccinated cohorts; incidence of cervical intraepithelial neoplasia 2 + was significantly reduced by up to 86% in the post-vaccine era. On the basis of these findings, HPV vaccination programs constitute a successful and effective public health initiative.

The early impact of human papillomavirus vaccination on anogenital warts in Québec, Canada.

In Québec province in Canada, a public school-based and catch-up HPV vaccination programs with the quadrivalent vaccine have been introduced in September 2008 for girls aged 9-17 years. We assessed the early impact of the HPV vaccination program on the incidence of anogenital warts (AGW) in the Quebec general population. We used the provincial health administrative data of the Régie de l'assurance maladie du Québec (RAMQ). AGW were identified either through a prescription of podofilox, or a medical procedure code specific to AGW, or a diagnostic code for viral warts followed by a prescription of imiquimod or fluorouracil. Sex- and age-specific incidence rates were calculated for pre-vaccination (2004-2007) and vaccination (2009-2012) periods. We found a significant decline of 45% and 19% in the incidence of AGWs among females aged 15-19 and 20-24 years, respectively. A decline of 21% was also seen among males aged 15-19 years. The median age at an episode of AGW increased from 27 years in 2004 to 31 years in 2012 among females and remained stable in males. Our findings indicate that the HPV public vaccination program is associated with an important reduction in the incidence of AGW among young females and males. The benefit is more pronounced among females 15-19 years of age, who were eligible for the public vaccination program. The observed decline among young males could be due to herd immunity and/or privately paid vaccination.

Recurrence of Human Papillomavirus External Genital Wart Infection Among High-Risk Adults in Montréal, Canada.

OBJECTIVES: The incidence of recurrent genital warts is not well characterized; this is especially true in a post-human papillomavirus (HPV) vaccination era. The objectives of this study were to assess the incidence of subsequent HPV-related external genital warts (EGW) episodes in high-risk male and female adults, as well as ascertain patient profile and disease characteristics, in a real-world Canadian sexual health clinical setting. METHODS: Retrospective chart review study conducted at Clinique médicale l'Actuel, a sexual health clinic in Montréal, Québec, Canada. Eligible patients were 18 to 45 years of age with a first diagnosis of EGW associated with a HPV infection between July 1, 2006, and June 30, 2012. RESULTS: A total of 400 first-episode EGW cases were identified. Up to 6 subsequent episodes were documented, with 194 (48.5%) patients reporting at least 1 subsequent EGW episode. Median time to first subsequent EGW episode was 3.97 years, and the incidence density rate for all subsequent episodes was 0.18/100 patient-years. Over 90% of patients reported clearance of the first subsequent episode, with median time to clearance of 0.30 years. Regardless of subsequent episode number, greater than 95% of patients received treatment, primarily cryotherapy, with high-risk sexual behavior reducing as number of episodes increased. CONCLUSIONS: Overall, a high rate of subsequent EGW episodes was observed in this high-risk population, despite high treatment rates and improvement in high-risk sexual behavior. These data, assessed in a prevaccination Québec health care system, may be compared with future EGW rates to assess the impact of a governmentally-funded HPV vaccination program.

Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: a systematic review.

OBJECTIVES: Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare yet aggressive disease caused by human papillomavirus (HPV). Although many newborns are likely exposed to HPV, few develop JoRRP and the clinical course of the disease varies from one child to another. This systematic review seeks to provide an up-to-date understanding of the risk factors for acquisition and severity. METHODS: We conducted a comprehensive literature search in EMBASE, MEDLINE and EBMR databases using various combinations of keywords related to JoRRP etiology, risk factors and severity. We also searched Google Scholar and the reference lists of eligible studies. Our search was limited to original studies published in French or English between 1995 and July 2012 and to patients under 20 years of age. RESULTS: Of 1362 citations, we retrieved 102 articles and found 14 additional studies. We retained 32 studies meeting inclusion criteria. All were observational and together included 2296 JoRRP cases. Risk factors could be classified mainly as maternal and birth history, viral genotype, and host factors. A history of genital warts during pregnancy and delivery was strongly linked to the development of JoRRP. Depending on ethnicity, specific human leukocyte antigen class II alleles and immune response factors were important determinants of JoRRP acquisition and severity. HPV-11 genotype and younger age at onset of JoRRP were important predictors of severity. CONCLUSIONS: Genetic and immunological profiles underlying the acquisition and clinical course are not readily modifiable. Thus, preventing condylomas in women of childbearing age could reduce the burden of this life-threatening disease.

Juvenile respiratory papillomatosis: risk factors for severity.

Juvenile recurrent respiratory papillomatosis is caused mainly by human papillomavirus genotypes 6 or 11, acquired at birth or during pregnancy from an infected mother. Recurrent respiratory papillomatosis is characterized by recurring warts growing most commonly in the larynx. Multiple surgical procedures and the risk of airway obstruction contribute to the devastating impact of this disease. Some children will go into remission after a few surgeries whereas others will require repeated interventions over several years. Further understanding of the risk factors associated with severity may contribute to tailored treatments. A retrospective study of cases diagnosed between January 1995 and December 2008 was conducted to study determinants of severe forms of juvenile recurrent respiratory papillomatosis. Demographic and clinical variables were abstracted from children's medical charts and mothers' delivery charts. Viral factors (HPV genotyping and viral load) were studied from archived biopsies. Specific HLA class II alleles and killer-cell immunoglobulin-like receptors genes were tested from saliva samples. Logistic regression was performed to identify risk factors for severity. Overall, 31 pediatric cases of recurrent respiratory papillomatosis were identified. The only significant factor associated with severe forms of recurrent respiratory papillomatosis was the maternal history of condylomas during pregnancy (OR: 12.05 [P=0.05]). The analysis failed to identify risk factors that could be used clinically to identify recurrent respiratory papillomatosis cases likely to take a severe course. Although too early to determine, vaccination against the HPV types involved most commonly in recurrent respiratory papillomatosis may provide the best hope to prevent severe forms of this disease.

Temporal trends in genital warts among individuals covered by the public prescription drug insurance plan in the province of Quebec, Canada, from 1998 to 2007.

OBJECTIVE: We assessed temporal trend in the incidence and prevalence of genital warts (GWs) in the province of Quebec, Canada, between 1998 and 2007 as a baseline for future assessment of the impact of Quebec human papillomavirus vaccination program. MATERIALS AND METHODS: Data on GWs were obtained from the linkage of the physician service claims and the public insurance drug plan databases. Genital warts were identified through a prescription of podofilox, a medical procedure code specific to GWs or a diagnosis code for viral warts followed by a prescription of imiquimod or fluorouracil within 2 weeks. An episode was considered incident if it was preceded by a 12-month interval period free of GWs care. RESULTS: During the study period, a total of 27,138 episodes of GWs occurred among 24,267 individuals. The age-standardized incidence rate increased over time in men and women. The highest incidence was observed in women aged 20 to 24 years (391.9/100,000) and in men aged 25 to 29 years (383.3/100,000). Similar trends in prevalence were observed. CONCLUSIONS: The incidence and prevalence of GWs has increased among the population covered by the public insurance drug plan in Quebec.