Strategies to accelerate the elimination of cervical cancer in British Columbia, Canada: a modelling study.

BACKGROUND: To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia. METHODS: We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC's historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050. RESULTS: HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon. INTERPRETATION: With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

Intention to Receive a COVID-19 Vaccine by HIV Status Among a Population-Based Sample of Women and Gender Diverse Individuals in British Columbia, Canada.

COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio-demographic, vaccine hesitancy, and psychological predictors of vaccine intention. Individuals (25-69 years) recruited from province-wide research cohorts and the general public completed an online survey examining COVID-19 impacts (August/2020-March/2021). In an analysis restricted to women and gender diverse participants (n = 5588), we compared intention to receive a recommended COVID-19 vaccine (Very likely/Likely vs Neutral/Unlikely/Very Unlikely) by self-reported HIV status. Logistic regression models assessed the independent effect of HIV status and other factors on COVID-19 vaccine intention. Of 5588 participants, 69 (1.2%) were living with HIV, of whom 79.7% were on antiretroviral therapy. In bivariate analyses, intention to vaccinate was significantly lower among PLWH compared to participants not living with HIV (65.2% vs 79.6%; OR 0.44; 95%CI 0.32-0.60). However, this association was not statistically significant after adjustment for ethnicity, income, education, and essential worker status (aOR 0.85; 95%CI 0.48-1.55). Among PLWH, those with greater vaccine confidence, positive attitudes towards the COVID-19 vaccine, and more strongly influenced by direct and indirect social norms to vaccinate had significantly higher odds of vaccine intention. Tailored messaging is needed to build vaccine confidence, address questions about vaccine benefits, and support informed vaccination decision-making to promote COVID-19 vaccine uptake among women and gender diverse people living with HIV.

Barriers To Accessing Contraception and Cervical and Breast Cancer Screening During COVID-19: A Prospective Cohort Study.

OBJECTIVE: This study sought to examine how access to contraception and cervical and breast cancer screening in British Columbia, Canada, has been affected by the COVID-19 pandemic. METHODS: From August 2020 to March 2021, 3691 female residents of British Columbia (age 25-69 y) participated in this study. We used generalized estimating equations to analyze the proportion of females accessing contraception and the proportion having difficulty accessing contraception across the different phases of pandemic control measures, and logistic regression to analyze attendance at cervical and breast cancer screening. We added sociodemographic and biological variables individually into the models. Self-reported barriers to accessing contraception and attending screening were summarized. RESULTS: During phases with the highest pandemic controls, self-reported access to contraception was lower (OR 0.94; 95% CI 0.90-0.98; P = 0.005) and difficulty with access was higher (OR 2.74; 95% CI 1.54-4.88; P = 0.001). A higher proportion of adults aged 25-34 years reported difficulty accessing contraception than those aged 35-39 years (P < 0.0001), and participants identifying as Indigenous had higher odds of access difficulties (OR 5.56; 95% CI 2.44-12.50; P < 0.001). Of those who required screening during the COVID-19 pandemic, 62% and 54.5% did not attend at least one of their cervical or breast screening appointments, respectively. Those with a history of breast cancer had significantly higher odds of self-reporting having attended their mammogram appointment compared with those without a history of breast cancer (OR 5.62; 95% CI 2.69-13.72; P < 0.001). The most common barriers to screening were difficulty getting an appointment and appointments being considered non-urgent. CONCLUSIONS: The COVID-19 pandemic has uniquely affected access to contraception and cancer screening participation for various subgroups. Self-reported data present potential avenues for mitigating barriers.

Population-Level Outcomes of Partner Notification Among Gay, Bisexual, and Other Men Who Report Sex With Men Diagnosed With Infectious Syphilis in British Columbia, Canada.

BACKGROUND: Syphilis testing, treatment, and partner notification (PN) are centrally coordinated in British Columbia (BC), Canada. Public health (PH) nurses (PHNs) contact almost all syphilis patients and either notify partners of syphilis exposure (PH-initiated PN) or support patients to notify their own partners (patient-initiated PN). In the context of an ongoing syphilis epidemic among gay, bisexual, and other men who report sex with men (gbMSM), we measured population-level yields and compared PN approaches to inform prevention and control efforts. METHODS: All gbMSM diagnosed with infectious syphilis in 2016 in BC were included. We calculated indicators of engagement with PN among patients and PN outcomes among notifiable partners using a cascade-of-care framework. χ2 Tests compared indicators between PN approaches. RESULTS: Of the 759 syphilis diagnoses, 85.4% (648/759) were among gbMSM and 94.7% (614/648) were treated within 30 days of testing (mean [SD], 5.5 [5.2] days). Among patients, 87.7% (568/648) discussed PN with PHNs and 49.5% (281/568) named at least 1 notifiable partner, for a total of 1094 partners (mean [SD], 3.9 [5.5] partners/patient). Compared with PH-initiated PN, patient-initiated PN resulted in a greater proportion of partners notified (70.1% [573/817] vs. 89.8% [211/235]; P = 1.88 × 10-9), but there was no difference in the proportion of partners tested and/or treated (90.2% [517/573] vs. 86.7% [183/211]; P = 0.203), and diagnosed (12.8% [66/517] vs. 16.4% [30/183]; P > 0.271). CONCLUSIONS: Public health- and patient-initiated PN had similarly high yields of partners tested and/or treated, and diagnosed, demonstrating that gbMSM can contribute to syphilis PN when supported by resource-equipped PHNs.

Long-term cervical precancer outcomes after a negative DNA- or RNA-based human papillomavirus test result.

BACKGROUND: Cervical cancer, a preventable disease associated with the human papillomavirus, is responsible for significant morbidity and mortality globally. Primary human papillomavirus testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. Screening programs must select the most appropriate assay from several available assays for their population. It is not yet known whether these assays perform equivalently in the long term, particularly among women with a negative human papillomavirus test result. This study aims to compare long-term safety after a negative human papillomavirus test result across both DNA- and RNA-based testing assays. OBJECTIVE: This study aimed to compare long-term high-grade cervical intraepithelial neoplasia (grade 2 or higher and grade 3 or higher) outcomes of 2 DNA-based assays (Digene Hybrid Capture 2 High-Risk HPV DNA Test and cobas 4800 HPV Test) and 1 messenger RNA-based assay (Aptima HPV Assay) using data from the Human Papillomavirus For Cervical Cancer Trial-DECADEl (FOCAL-DECADE) cohort, by first comparing the positive and negative rates between the assays and then investigating the cumulative incidence of cervical intraepithelial neoplasia grade 2 and higher and grade 3 or higher detection among participants in the FOCAL DECADE cohort over follow-up according to human papillomavirus testing assays. STUDY DESIGN: The FOCAL Trial was a randomized controlled trial that evaluated human papillomavirus testing for primary cervical cancer screening. The FOCAL-DECADE cohort subsequently followed FOCAL Trial participants passively through the British Columbia Cervix Screening Program Database for approximately 10 years after the FOCAL Trial study exit to examine the rates of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher. For this study, eligible participants had baseline human papillomavirus-negative results from at least 1 assay and had 1 or more cytologic screens after baseline (9509 participants for DNA-based and 3473 participants for DNA- vs RNA-based assay comparisons). We constructed cumulative incidence curves and compared the hazard ratios for cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher detection according to the assays. RESULTS: Over 10 years of follow-up, the cumulative incidence of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ between the DNA-based assays (hazard ratio, 0.95; 95% confidence interval, 0.84-1.06; P=.35 and hazard ratio, 0.82; 95% confidence interval, 0.66-1.01; P=.06 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively) or between the DNA- and RNA-based assays (hazard ratio, 0.97; 95% confidence interval, 0.87-1.06; P=.48 and hazard ratio, 0.94; 95% confidence interval, 0.79-1.13; P=.52 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively). CONCLUSION: Among participants who tested negative for human papillomavirus at baseline, the long-term risk of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ regardless of whether DNA- or RNA-based human papillomavirus testing assays were used. Screening program decision makers can be confident that for women who test negative for human papillomavirus, DNA- and RNA-based assays exhibit similar cervical intraepithelial neoplasia grade 2 or higher outcomes over several years.

Intention to receive a COVID-19 vaccine: results from a population-based survey in Canada.

BACKGROUND: The success of any COVID-19 vaccine program ultimately depends on high vaccine uptake. This study determined overall intention to receive a COVID-19 vaccine and identified factors that predict intentions to be vaccinated against COVID-19 in Canada, specifically in key priority groups identified by the American Committee on Immunization Practice (ACIP) and the National Advisory Committee on Immunization (NACI) for early immunization. METHODS: Individuals from research cohorts from the general population of British Columbia aged 25-69 were invited complete an online survey based on validated scales and theoretical frameworks to explore intention to receive a COVID-19 vaccine. Two multivariable logistic regression models were conducted to determine factors associated with intention to receive the COVID-19 vaccine. RESULTS: Of 4948 respondents, 79.8% intended to receive a COVID-19 vaccine. In multivariable modeling, respondents who intended to receive the vaccine had higher vaccine attitudinal scores (p <  0.001), reported greater influence of direct social norms (p = 0.001), and indirect social norms, including their family physician (p = 0.024), and Provincial Health Officer (p = 0.011). Older individuals (> 60 years) were more likely to intend to receive the vaccine, while females (95%CI 0.57,0.93), those with less than high school education (95%CI 0.5,0.76), those who self-identified as non-white (95%CI 0.60,0.92), self-identified as Indigenous (95%CI 0.36,0.84) and essential non-health care workers (95%CI 0.59,0.86) had lower adjusted odds of intending to receive a COVID-19 vaccine. CONCLUSIONS: To optimize vaccine coverage, public health should focus on key messages around vaccine safety and benefit, and leverage trusted practitioners for messaging. As certain key populations identified by NACI and ACIP for early immunization report a lower intention to vaccinate, there is a need for in-depth education and support for these communities to ensure optimal uptake.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening.

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

BACKGROUND: In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM. METHODS: Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression. RESULTS: There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort. CONCLUSIONS: The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial.

Human papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case-control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25-65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50

Population-level sexual behaviours in adolescent girls before and after introduction of the human papillomavirus vaccine (2003-2013).

BACKGROUND: The human papillomavirus (HPV) vaccine is delivered widely through school-based immunization programs. Some groups have expressed concern that HPV vaccination programs will result in an increase in sexual risk-taking behaviours among adolescents. We aimed to evaluate population-level changes in sexual behaviours before and after implementation of the school-based HPV vaccination program in British Columbia. METHODS: In 2008, a school-based HPV vaccination program for girls was introduced in British Columbia. Using data from the BC Adolescent Health Survey - a longitudinal provincial survey administered in schools to capture adolescent physical and emotional health indicators, we conducted a linear trend analysis on sexual health behaviours and risk factors in adolescent girls before and after the implementation of vaccination for HPV (2003, 2008 and 2013). RESULTS: We analyzed data for 298 265 girls who self-identified as heterosexual. The proportion of girls reporting ever having sexual intercourse decreased from 21.3% (2003) to 18.3% (2013; adjusted odds ratio [OR] 0.79). Self-report of sexual intercourse before the age of 14 years decreased significantly from 2008 to 2013 (adjusted OR 0.76), as did reported substance use before intercourse (adjusted OR for 2003-2013 0.69). There was no significant change in the number of sexual partners reported (2003-2013). Between 2003 and 2013, girls' reported use of contraception and condoms increased, while pregnancy rates decreased. INTERPRETATION: Since the implementation of school-based HPV vaccination program in BC, sexual risk behaviours reported by adolescent girls either reduced or stayed the same. These findings contribute evidence against any association between HPV vaccination and risky sexual behaviours.

Effect of human papillomavirus vaccination on sexual behaviour among young females.

Question At the time of implementation of human papillomavirus (HPV) vaccine immunization programs, concerns were raised by parents, clinicians, and public health professionals about HPV vaccination possibly leading to riskier sexual health choices among young females. If HPV vaccination influences sexual behaviour among vaccinated females, this might influence the effect of HPV vaccination programs. What is known about the effects of the HPV vaccination program on sexual behaviour among young females?Answer Human papillomavirus vaccination has not been associated with increased sexual risk behaviour among young females. However, currently available studies have some important limitations, and future studies should focus on a longitudinal design that includes a prevaccination baseline measurement, adjustment for possible confounders, and measurement of both clinical indicators and behavioural outcomes.

Cost-effectiveness of cervical cancer screening methods in low- and middle-income countries: A systematic review.

The incidence of cervical cancer in low- and middle-income countries (LMICs) is five times higher than that observed in high-income countries (HICs). This discrepancy is largely attributed to the implementation of cytology-based screening programmes in HICs. However, due to reduced health system infrastructure requirements, HPV testing (self- and provider-collected) and visual inspection with acetic acid (VIA) have been proposed as alternatives that may be better suited to LMICs. Knowing the relative value of different screening options can inform policy and the development of sustainable prevention programs. We searched MEDLINE and EMBASE for English language publications detailing model-based cost-effectiveness analyses of cervical cancer screening methods in LMICs from 2000 to 2016. The main outcome of interest was the incremental cost-effectiveness ratio (ICER). Quantitative data were extracted to compare commonly evaluated screening methods and a descriptive review was conducted for each included study. Of the initial 152 articles reviewed, 19 met inclusion criteria. Generally, cytology-based screening was shown to be the least effective and most costly screening method. Whether provider-collected HPV testing or VIA was the more efficient alternative depended on the cost of the HPV test, loss to follow-up and VIA test performance. Self-collected HPV testing was cost-effective when it yielded population coverage gains over other screening methods. We conclude that HPV testing and VIA are more cost-effective screening methods than cytology in LMICs. Policy makers should consider HPV testing with self-collection of samples if it yields gains in population coverage.

HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV-based primary screening to liquid-based cytology for cervical cancer.

Complete Round 1 data (baseline and 12-month follow-up) for HPV FOCAL, a randomized trial establishing the efficacy of HPV DNA testing with cytology triage as a primary screen for cervical cancer are presented. Women were randomized to one of three arms: Control arm - Baseline liquid-based cytology (LBC) with ASCUS results triaged with HPV testing; Intervention and Safety arms - Baseline HPV with LBC triage for HPV positives. Results are presented for 15,744 women allocated to the HPV (intervention and safety combined) and 9,408 to the control arms. For all age cohorts, the CIN3+ detection rate was higher in the HPV (7.5/1,000; 95%CI: 6.2, 8.9) compared to the control arm (4.6/1,000; 95%CI: 3.4, 6.2). The CIN2+ detection rates were also significantly higher in the HPV (16.5/1,000; 95%CI: 14.6, 18.6) vs. the control arm (10.1/1,000; 95%CI: 8.3, 12.4). In women ≥35 years, the overall detection rates for CIN2+ and CIN3+ were higher in the HPV vs. the control arm (CIN2+:10.0/1,000 vs. 5.2/1,000; CIN3+: 4.2/1,000 vs. 2.2/1,000 respectively, with a statistically significant difference for CIN2+). HPV testing detected significantly more CIN2+ in women 25-29 compared to LBC (63.7/1,000; 95%CI: 51.9, 78.0 vs. 32.4/1,000; 95%CI: 22.3, 46.8). HPV testing resulted in significantly higher colposcopy referral rates for all age cohorts (HPV: 58.9/1,000; 95%CI: 55.4, 62.7 vs. CONTROL: 30.9/1,000; 95%CI: 27.6, 34.6). At completion of Round 1 HPV-based cervical cancer screening in a population-based program resulted in greater CIN2+ detection of across all age cohorts compared to LBC screening.

Self-collection based HPV testing for cervical cancer screening among women living with HIV in Uganda: a descriptive analysis of knowledge, intentions to screen and factors associated with HPV positivity.

BACKGROUND: Women living with HIV (WHIV) are disproportionately impacted by cervical dysplasia and cancer. The burden is greatest in low-income countries where limited or no access to screening exists. The goal of this study was to describe knowledge and intentions of WHIV towards HPV self-collection for cervical cancer screening, and to report on factors related to HPV positivity among women who participated in testing. METHODS: A validated survey was administered to 87 HIV positive women attending the Kisenyi Health Unit aged 30-69 years old, and data was abstracted from chart review. At a later date, self-collection based HPV testing was offered to all women. Specimens were tested for high risk HPV genotypes, and women were contacted with results and referred for care. Descriptive statistics, Chi Square and Fischer-exact statistical tests were performed. RESULTS: The vast majority of WHIV (98.9%) women did not think it necessary to be screened for cervical cancer and the majority of women had never heard of HPV (96.4%). However, almost all WHIV found self-collection for cervical cancer screening to be acceptable. Of the 87 WHIV offered self-collection, 40 women agreed to provide a sample at the HIV clinic. Among women tested, 45% were oncogenic HPV positive, where HPV 16 or 18 positivity was 15% overall. CONCLUSIONS: In this group of WHIV engaged in HIV care, there was a high prevalence of oncogenic HPV, a large proportion of which were HPV genotypes 16 or 18, in addition to low knowledge of HPV and cervical cancer screening. Improved education and cervical cancer screening for WHIV are sorely needed; self-collection based screening has the potential to be integrated with routine HIV care in this setting.

Disease detection and resource use in the safety and control arms of the HPV FOCAL cervical cancer screening trial.

BACKGROUND: The HPV FOCAL Trial is a RCT comparing human papilloma virus (HPV) with Liquid Based Cytology (LBC) screening for cervical cancer. Results are presented for the comparison of the Safety and Control arms after two rounds. METHODS: HPV FOCAL included randomisation of women aged 25-65 into the Safety arm, where they were initially screened with HPV and the Control arm, where they received entry screening with LBC, with both arms screened again with LBC at 24 months. RESULTS: There are 6203 (Safety) and 6075 (Control) women included in this analysis. For the Safety vs Control arms, Round 1 screening resulted in increased detection of cervical intraepithelial neoplasia 2 or worse (CIN2+),15.3 vs 10.4 per 1000, RR=1.48 (95%CI=1.08-2.03) and higher colposcopy referral rates, 5.6% vs 3.2%. LBC screening at 24 months resulted in similar colposcopy referral rates, 1.5% vs 1.9%, and decreased CIN2+ detection, 2.0 vs 4.7 per 1000, RR=0.43 (95%CI=0.21-0.88) in the Safety vs Control arms. CIN2+ detection and colposcopy referral rates declined with increasing age in both arms. One round of HPV screening detected similar levels of CIN2+ as two rounds of LBC screening. INTERPRETATION: CIN2+ detection at 2 years was lower in those screened by HPV, indicating an improved 2-year negative predictive value of the HPV test.

Correlates of women's intentions to be screened for human papillomavirus for cervical cancer screening with an extended interval.

BACKGROUND: High-risk HPV DNA testing has been proposed as a primary tool for cervical cancer screening (HPV-CCS) as an alternative to the Papanicolaou cytology- method. This study describes factors associated with women's intentions to attend cervical cancer screening if high-risk HPV DNA testing (HPV-CCS) was implemented as a primary screening tool, and if screening were conducted every 4 years starting after age 25. METHODS: This online survey was designed using the Theory of Planned Behaviour to assess factors that impact women's intentions to attend HPV-CCS among women aged 25-69 upon exit of the HPV FOCAL trial. Univariate and regression analyses were performed to compare the demographic, sexual history, and smoking characteristics between women willing and unwilling to screen, and scales for intention to attend HPV-CCS. A qualitative analysis was performed by compiling and coding the comments section of the survey. RESULTS: Of the 981 women who completed the survey in full, only 51.4 % responded that they intended to attend HPV-CCS with a delayed start age and extended screening interval. Women who intended to screen were more likely to have higher education (AOR 0.59, 95 % CI [0.37, 0.93]), while both positive attitudes (AOR 1.26, 95 % CI [1.23, 1.30]) and perceived behavior control (AOR 1.06, 95 % CI [1.02, 1.10]) were significant predictors of intention to screen. Among women who provided comments in the survey, a large number of women expressed fears about not being checked more than every 4 years, but 12 % stated that these fears may be alleviated by having more information. CONCLUSIONS: Acceptability of increased screening intervals and starting age could be improved through enhanced education of benefits. Program planners should consider measures to assess and improve women's knowledge, attitudes and beliefs prior to the implementation of new screening programs to avoid unintended consequences.

Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis.

We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15-22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency's population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15-22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15-17 years decreased significantly from 0.91 (95% CI: 0.86-0.98 p < 0.01) to 0.36 (95% CI: 0.18-0.73 p < 0.01). During the same time period, no similar reduction was found in young women 18-22 years. After introduction of HPV vaccine program, IRR for CIN2+ in young women 15-17 was significantly reduced for CIN2+ (0.14; 95% CI: 0.04- 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02-0.54; p < 0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15-17 years in British Columbia after the introduction of the HPV vaccine in young women despite vaccine uptake levels below 70%.

Current status of human papillomavirus vaccination.

PURPOSE OF REVIEW: In this article, we review the impact of the quadrivalent and bivalent prophylactic human papillomavirus (HPV) vaccines on HPV infection and disease, review alternative vaccine dosing schedules, the vaccination of men and the nine-valent HPV vaccine. RECENT FINDINGS: HPV vaccines have had dramatic impacts on the prevalence of targeted HPV types (6,11,16 and 18), genital warts and precancerous cervical lesions. Population coverage would be facilitated by adopting two-dose schedules, with recent findings that two-dose schedules in young adolescents are as immunogenic as three doses in young adults. Extension of vaccination to men, particularly for men who have sex with men, could further reduce population prevalence of HPV and provide direct protection to men against genital warts and anal, penile and oropharyngeal cancers. The nine-valent HPV vaccine has demonstrated equivalent protection against the four types in the quadrivalent vaccine and high efficacy against the next five commonest causes of cervical cancer (HPV types 31,33,45,52 and 58). If cost-effective, it may extend the spectrum of protection against cervical cancer available through vaccination. SUMMARY: HPV vaccination is an effective strategy for reducing the burden of HPV-related disease. New schedules, target populations and vaccines promise to expand this potential further.

Comparison of the Roche cobas® 4800 and Digene Hybrid Capture® 2 HPV tests for primary cervical cancer screening in the HPV FOCAL trial.

BACKGROUND: HPV FOCAL is a randomized trial (ISRCTN79347302, registered 20 Apr 2007) comparing high-risk (hr) HPV testing vs. liquid-based cytology (LBC) for cervical cancer screening of women aged 25-65. We compared the Digene Hybrid Capture® 2 High-Risk HPV DNA Test® (HC2) and the Roche cobas® 4800 HPV Test (COBAS) for primary screening. METHODS: Women (n=6,172) were screened at baseline by HC2 and COBAS and by LBC 24 months later. We assessed HPV genotyping and reflex LBC for colposcopy triage of baseline HPV positive women. RESULTS: Overall HC2/COBAS agreement was 96.1% (kappa 0.75) and positive agreement was 77.5%. Baseline CIN2 and CIN3+ rates based on HPV screening were 8.6/1,000 and 6.6/1,000 respectively; 24 month rates were 0.7/1,000 and 0.4/1,000 (LBC screening). HC2 and COBAS were concordant positive for 91% of round 1 CIN2 and 98% of CIN3+. CIN3+ was significantly associated with HPV 16 (Odds Ratio [OR] 5.11; 95% confidence interval [CI] 2.30, 11.37), but not HPV 18 (OR 2.62; 95% CI 0.73, 9.49), vs. non-HPV 16/18 HPV at baseline. There was no significant association between HPV genotype and CIN2. CIN3+ was significantly more likely for high-grade (OR 5.99; 95% CI 2.53, 14.18), but not low-grade (OR 0.54; 95% CI 0.20, 1.49), vs. negative LBC. No significant association was observed between LBC grade and CIN2. HPV 16 and 18 were associated with 33% of CIN2 and 68% of CIN3+ identified at baseline. CONCLUSIONS: For hrHPV positive women, abnormal reflex LBC is appropriate for colposcopy triage. In addition, immediate referral of women with HPV 16/18 and normal cytology may allow for earlier detection of CIN2+ lesions which would not be detected until after follow-up testing.