Ensuring a Successful Transition From Cytology to Human Papillomavirus-Based Primary Cervical Cancer Screening in Canada by Investigating the Psychosocial Correlates of Women's Intentions: Protocol for an Observational Study.

BACKGROUND: The human papillomavirus (HPV) test has emerged as a significant improvement over cytology for primary cervical cancer screening. In Canada, provinces and territories are moving toward implementing HPV testing in cervical cancer screening programs. Although an abundance of research exists on the benefits of HPV-based screening, there is a dearth of research examining women's understanding of HPV testing. In other countries, failure to adequately address women's concerns about changes has disrupted the implementation of HPV-based screening. OBJECTIVE: The aims of the multipart study described in this paper are to develop psychometrically valid measures of cervical cancer screening-related knowledge, attitudes, and beliefs; to examine the feasibility of a questionnaire examining psychosocial factors related to HPV-based screening; and to investigate psychosocial correlates of women's intentions to participate in HPV-based screening. METHODS: We conducted a web-based survey (study 1) of Canadian women to assess the acceptability and feasibility of a questionnaire, including the validation of scales examining cervical cancer knowledge, HPV testing knowledge, HPV testing attitudes and beliefs, and HPV test self-sampling attitudes and beliefs. Preferences for cervical cancer screening were assessed using the best-worst scaling methodology. A second web-based survey (study 2) will be administered to a national sample of Canadian women between June 2022 and July 2022 using the validated scales. Differences in the knowledge, attitudes, beliefs, and preferences of women who are currently either underscreened or adequately screened for cervical cancer will be examined through bivariate analyses. Multinomial logistic regression will be used to estimate the associations between psychosocial and sociodemographic factors and intentions to undergo HPV-based screening. RESULTS: Between October 2021 and November 2021, a total of 1230 participants completed the questionnaire in study 1, and 1027 (83.49%) responses were retained after data cleaning methods were applied. Feasibility was comparable with similar population-based surveys in terms of survey length, participant attrition, and the number of participants excluded after data cleaning. As of May 2022, analysis of study 1 is ongoing, and results are expected to be published in the summer of 2022. Data collection is expected to begin for study 2 in the summer of 2022. Results are expected to be published between late 2022 and early 2023. CONCLUSIONS: Findings will provide direction for Canadian public health authorities to align guidelines to address women's concerns and optimize the acceptability and uptake of HPV-based primary screening. Validated scales can be used by other researchers to improve and standardize the measurement of psychosocial factors affecting HPV test acceptability. Study results will be disseminated through peer-reviewed journal articles; conference presentations; and direct communication with researchers, clinicians, policy makers, media, and specialty organizations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38917.

Human papillomavirus seroprevalence and seroconversion following baseline detection of nine human papillomavirus types in young women.

BACKGROUND: Estimates of the humoral immune response to incident human papillomavirus (HPV) infections are limited. METHODS: In this post hoc analysis of 3875 women aged 16-23 years from a 4-valent HPV vaccine trial (NCT00092482), HPV seroprevalence on day 1 was measured with a 9-valent HPV (HPV 6/11/16/18/31/33/45/52/58) competitive Luminex immunoassay and compared with cervical/external genital HPV detection by polymerase chain reaction. In the control group, among women who were HPV DNA‒negative on day 1, seroconversion following initial HPV detection was estimated using Kaplan-Meier methods. RESULTS: Type-specific HPV seropositivity among women with no day 1 cervical/external genital HPV detection was 0.6%-3.6%. Women with any 9-valent HPV (9vHPV) cervical/external genital detection (796/3875; 20.5%) had concordant seropositivity ranging from 13.4% (HPV 45) to 38.5% (HPV 6). Among women in the control group who were negative for all HPV types on day 1, seroconversion by month 30 after initial detection ranged from 29% (HPV 45) to 75% (HPV 16). CONCLUSIONS: Humoral immune response to HPV is variable and dynamic, depending on type-specific exposure. This longitudinal analysis provides insight into the relationship between incident infection and seropositivity. CLINICALTRIALS: gov; NCT00092482 https://clinicaltrials.gov/ct2/show/NCT00092482.

A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada.

This study models the impact of using two different types of high-risk (HR) human papillomavirus (HPV) tests: mRNA (Aptima) and DNA (Hybrid Capture 2) as part of a hypothetical primary HPV screening program in Ontario, Canada. Outcomes were the costs of the screening program, and number of colposcopies, HPV tests and cytology tests. Results were estimated for one cohort going through the screening algorithm. A decision tree model was adapted from a published UK study, with inputs drawn from published Canadian data for the probabilities through the model, costs, demographic, and screening data from Ontario. Sensitivity and scenario analyses explored uncertainty in the model inputs and assumptions. Results indicated that screening using an mRNA test could yield cost savings of CAD $4,007,266 (95% credibility interval [CI]: -7,866,251 - 8,035) compared to using a DNA test, with 10,639 (95% CI: 10,170 - 11,094) fewer women undergoing unnecessary colposcopies, and reductions in unnecessary HR-HPV and cytology tests. The HR-HPV test comprised the largest percentage of the costs saved, and the probability of being HPV positive in the first year had the biggest impact on results. These results indicate that the choice of HR-HPV test is important when implementing a primary HPV screening program to avoid unnecessary resource use and cost, which will benefit both women and healthcare providers.

A National Survey of Canadian Adults on HPV: Knowledge, Attitudes, and Barriers to the HPV Vaccine.

OBJECTIVE: Identifying human papillomavirus (HPV) vaccination motivators and barriers among adults could lead to new approaches to improve HPV vaccination rates in non-pediatric populations. This Canadian survey aimed to assess current knowledge of, attitudes towards, and barriers to the HPV vaccine among the general public. METHODS: An online panel was used to survey HPV unvaccinated women (n = 802) and vaccinated women (n = 250) 18 to 45 years old, as well as 18- to 26-year-old men (n = 200), in May and June 2016. A 16-item questionnaire collected data on sociodemographic factors, health-seeking behaviours, knowledge of HPV infection and its consequences, and the HPV vaccine. Data were stratified by sex and by vaccination status among women. RESULTS: The majority of individuals somewhat or strongly agreed that vaccination is an important aspect of disease prevention (vaccinated women, 93%; unvaccinated women, 85%; and men, 59%). However, a high proportion of patients were concerned about vaccine safety (vaccinated women, 26%; unvaccinated women, 40%; and men, 36%). Moreover, 58% to 61% of participants were generally cautious about taking any vaccine. The number one reported barrier to vaccination was not having a recommendation from a doctor (38%). Cost was seen as a barrier by only 18% to 20% of participants. CONCLUSION: Canadian participants show a broad diversity in HPV knowledge and regarding barriers to vaccination. The youngest populations (vaccinated women and men) showed higher levels of knowledge regarding HPV.

A National Survey of Canadian Physicians on HPV: Knowledge, Barriers, and Preventive Practices.

OBJECTIVE: Physicians are the sole prescribers of the human papillomavirus (HPV) vaccine for adults in Canada. This survey of Canadian physicians aimed to explore knowledge, barriers, and preventive practices regarding HPV vaccination. METHOD: A survey of general practitioners (GPs) (n = 337) and obstetrician/gynaecologists (OB/GYNs) (n = 81) was conducted in May and June 2016 using an online panel. Demographic data and information pertaining to HPV knowledge, attitudes, and vaccination practices were collected by using a 22-item questionnaire. RESULTS: A total of 83% of GPs recommended or administered HPV vaccine to adults. Among physicians, 99% to 100% strongly agreed that vaccination is an important aspect of disease prevention. Physicians were rarely concerned about vaccine safety (5%-11%). Cost was seen as the number one barrier by 92% to 95% of physicians. Physicians rated consumers' understanding of HPV to be low (11%-14%, very good; and 49%-56%, somewhat good knowledge). Among physicians, 60% to 66% of said they routinely discussed HPV vaccination with patients. Female physicians demonstrated greater knowledge of HPV than their male counterparts. CONCLUSION: GPs and obstetrician/gynaecologists routinely recommend and administer the HPV vaccine to patients. The majority of physicians showed high levels of knowledge regarding HPV vaccine and associated cancers; however, perceived barriers of cost may limit recommendations for vaccination, particularly among older women or men.

HPV Screening and Vaccination Strategies in an Unscreened Population: A Mathematical Modeling Study.

Human papillomavirus (HPV), a sexually transmitted infection, is the necessary cause of cervical cancer, the third most common cancer affecting women worldwide. Prevention and control strategies include vaccination, screening, and treatment. While HPV prevention and control efforts are important worldwide, they are especially important in low-income areas with a high infection rate or high rate of cervical cancer. This study uses mathematical modeling to explore various vaccination and treatment strategies to control for HPV and cervical cancer while using Nepal as a case study. Two sets of deterministic models were created with the goal of understanding the impact of various prevention and control strategies. The first set of models examines the relative importance of screening and vaccination in an unscreened population, while the second set examines various screening scenarios. Partial rank correlation coefficients confirm the importance of screening and treatment in the reduction of HPV infections and cancer cases even when vaccination uptake is high. Results also indicate that less expensive screening technologies can achieve the same overall goal as more expensive screening technologies.

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.

Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: CLINICALTRIALS.GOV,: NCT00092521 and NCT00092534.

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.

Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region.

BACKGROUND: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region METHODS: Women ages 15-26 and 24-45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. RESULTS: Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for 25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia. Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3. CONCLUSIONS: The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3.

Associations of Anogenital Low-Risk Human Papillomavirus Infection With Cancer and Acquisition of HIV.

α-Mucosal human papillomavirus (HPV) types are implicated in a range of clinical conditions and categorized as "low-risk" (LR) and "high-risk" (HR) types according to their degree of association with cervical cancers. The causative role of LR HPV infection in the development of anogenital warts and in low-grade squamous intraepithelial lesions is well established. In addition, there is a growing body of evidence that infection with LR HPV types may be associated with an elevated risk of cancers and potentiation of coinfections. Prospective and case-control studies consistently report a higher risk of anogenital cancers in men and women with a history of anogenital warts. Based on currently available evidence, this higher risk may be due to shared exposure to HR HPV types or an underlying immune impairment, rather than a direct role of LR HPV types in subsequent cancer risk. Data also suggest that infection with LR HPV, HR HPV, or both may increase the risk of HIV acquisition, although the relative contribution of different HPV types is not yet known. There is also evidence implicating HPV clearance, rather than HPV infection, in increased risk of HIV acquisition.

Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease.

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.