Singaporean men's knowledge of cervical cancer and human papillomavirus (HPV) and their attitudes towards HPV vaccination

Little is known of men's knowledge of cervical cancer and its links with human papillomavirus (HPV), or of their attitudes and beliefs about HPV vaccination. This is despite men's sexual behaviour contributing to HPV transmission and their potential role in deciding whether their children are vaccinated against HPV. To address this, a comprehensive survey was conducted in Singapore where plans are underway for an HPV vaccination program. A representative sample of 930 Singaporean men was found to have moderate knowledge of cervical cancer but poor knowledge and awareness of HPV. Although these men showed strong support for HPV vaccination, overall findings highlight the importance of including men in education campaigns that aim to decrease the incidence of cervical and other HPV-related cancers and to increase the uptake of HPV vaccination.     

The clinical benefit and cost-effectiveness of human papillomavirus vaccination for adult women in the Netherlands

Background

The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17-25 years in 2010.

Methods

The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status.

Results

In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17-25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status.

Conclusion

The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17-25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.     

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: A transmission-dynamic modeling study

Background

The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions.

Methods

We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs ($CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations.

Results

Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, $95/dose), using the quadrivalent and bivalent vaccines is estimated to cost $15,528 [12,056;19,140] and $20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is $32 [17;46] (using a $40,000/QALY-gained threshold). Results were most sensitive to discounting, time-horizon, differences in durations of protection and anogenital warts burden.

Conclusions

Vaccinating pre-adolescent girls against HPV is predicted to be highly cost-effective. If equally priced, the quadrivalent is the most economically desirable vaccine. However, ultimately, the most cost-effective HPV vaccine will be determined by their relative price.     

Community-based household assessment of human papillomavirus (HPV) vaccination coverage and acceptability – HPV vaccine demonstration program,Cambodia – 2017

Background

In 2017, the Cambodia Ministry of Health introduced human papillomavirus (HPV) vaccine through primarily school-based vaccination targeting 9-year-old girls. Vaccination with a two-dose series of HPV vaccine took place in six districts in two provinces as a demonstration program, to better understand HPV vaccine delivery in Cambodia.

Planning for human papillomavirus (HPV) vaccination in sub-Saharan Africa: A modeling-based approach

Background

Human papillomavirus (HPV) vaccines have the potential to reduce cervical cancer incidence and mortality, particularly in the parts of the developing world that bear the greatest burden of disease. This research sought to predict the impact and cost-effectiveness of an HPV vaccination program in an example low-resource country with a high burden of cervical cancer: Mali, West Africa.

Methods

Novel compartmental mathematical models projected the impact of adolescent HPV vaccination in urban and rural areas of Mali. The models accounted for two high-risk vaccine-types: HPV 16 and 18. We then attached comprehensive real cost and cost-effectiveness estimates.

Results

Our models predict that HPV vaccination in Mali will reduce cervical cancer burden by a factor roughly equal to vaccine coverage. A point vaccination program was simulated in a cohort of 333,146 urban and 588,982 rural Malian women, age 10–14. Vaccination of 50% of girls reduced the peak prevalence of HPV 16/18 to 5.0% in the urban setting and 9.6% in the rural setting, down from 11.7% and 22.0%, respectively, with no vaccination. The 50% vaccination scenario averted 1145 cervical cancer deaths in the urban group and 2742 in the rural group. The cost per discounted life-year saved in this scenario was 1030 US dollars (urban) and 725 dollars (rural). The cost per life-year saved was higher at 90% coverage, but was still in the range of a “cost-effective” public health intervention.

Conclusions

This research yielded the most comprehensive real cost estimates of HPV vaccination yet published for sub-Saharan Africa. Our models indicate that HPV vaccination in Mali will be cost-effective when introduced. To maximize the benefit using limited resources, vaccination programs may begin with a target coverage of about 50%. We anticipate that costs of reaching late adopters after the First Vaccinated Wave of vaccination will be higher, but worthwhile.     

Human papillomavirus (HPV) vaccine uptake and completion at an urban hospital

Background

Despite the benefit of the human papillomavirus (HPV) vaccine in preventing cervical cancer, fewer than half of eligible young women in the United States have initiated the three-vaccine series. Among those who initiate HPV vaccination, large proportions do not complete the three-dose regimen.

Purpose

To evaluate racial and health insurance-related disparities in HPV vaccination.

Methods

We analyzed outpatient claims data for 8069 patients, ages 9-26 years, who had gynecologic visits at the University of Maryland Medical Center outpatient clinic from August 2006 to January 2010.

Results

Thirty-five percent of our sample initiated the vaccine series, including 91% of those ages 9-13. Only 11% of the sample and 33% of the 9-13 age group completed the 3 dose series. A higher proportion of blacks than whites (38% vs. 32%; p < 0.01) initiated, and 11% and 12%, respectively, of each race completed. Lower age was strongly correlated with uptake. After adjustment for insurance, blacks were less than half as likely as whites to complete the series in all age groups, and had 0.35 the odds (95% CI 0.26-0.46) of adherence. The uninsured had much lower race-adjusted odds than insured groups for initiation, but had similar adherence rates. Publicly insured individuals were more likely than the privately insured to complete all 3 doses.

Conclusions

Of the population of gynecologic service seekers seen at our university-based outpatient practice clinics, a significant minority initiate but do not complete the HPV vaccine series. More blacks than whites initiate the series, but similar proportions of the two races complete. Lack of insurance appears to be a major barrier to initiation, despite free vaccination programs.     

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

Background

Vaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+.

Methods

As part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’.

Results

Among 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR = .67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p = .001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p = .001) and publicly compared to privately insured women (38.1% vs. 17.4%, p < .0001).

Conclusion

We found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.     

Knowledge differences between male and female university students about human papillomavirus (HPV) and cervical cancer: Implications for health strategies and vaccination

Knowledge about HPV and cervical cancer (CC) depends on several factors such as gender and education, which brings implications for health strategies and vaccination. A survey was conducted in Portugal with a representative sample of 1706 university students. Only 55.4% (n = 945) had already heard of HPV, although 88.3% (n = 834) from that know that is a risk factor for CC. 89% students (n = 841) wants to be vaccinated against it, but only 13.8% stated as main reason to be vaccinated “prevention of the disease”. Mean scores of knowledge were calculated. Statistical differences were found, regarding “CC knowledge”, in gender (p < 0.001) and between health sciences schools and non-health sciences schools (p < 0.001). Differences regarding the study area in “knowledge and beliefs of HPV” (p < 0.001) and in “relation between HPV and CC” (p < 0.001) were found. Therefore, these differences may help to develop effective strategies that lead to decline CC incidence and mortality.     

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: A transmission-dynamic modelling study

Background

Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada.

Methods

We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost.

Findings

Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900–24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated.

Interpretation

Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.     

Cost-effectiveness of a tetravalent human papillomavirus vaccine in Germany

Aim  Clinical trials have demonstrated the efficacy of the tetravalent human papillomavirus (HPV) vaccination in the prevention of cervical cancer and genital warts associated with HPV types 6, 11, 16 and 18. We used an empirically calibrated Markov cohort model of the natural history of HPV to assess the cost-effectiveness of the vaccine administered to 12-year-old girls alongside existing cervical screening programmes in Germany. Subjects and methods  The model estimated cervical cancer (CC), cervical intraepithelial neoplasia (CIN) and genital wart lifetime risks and total lifetime health care costs, life years gained and quality-adjusted life years (QALY) gained. The analysis was conducted from the perspective of the German health care payer. Results  In the base case (considering a lifetime duration of protection and 100% efficacy) it was estimated that 2,835 cervical cancer cases and 679 deaths could be prevented among a cohort of 400,000, at an incremental cost per QALY gained of 10,530 €. A total of 120 girls needed to be vaccinated to prevent 1 case of CC. Cost-effectiveness is sensitive to a duration of protection of less than 20 years and to the discount rate for costs and benefits. Conclusion  A policy of vaccinating adolescent girls has been recommended by the German Standing Committee on Vaccinations. This study has demonstrated that such a policy is cost-effective based on thresholds of cost-effectiveness that apply in Germany.     

Knowledge of human papillomavirus (HPV) and HPV vaccination: An international comparison

Since vaccination against human papillomavirus (HPV) became available, awareness of HPV has dramatically increased. Implementation of a vaccine program varies internationally yet no studies have explored the influence this has on the public's knowledge of HPV. The present study aimed to explore differences in awareness of HPV and HPV knowledge across three countries: The US, UK and Australia.     

Completion of the human papillomavirus (HPV) vaccine series among males with private insurance between 2006 and 2009

Little is known about initiation and completion among males who received the HPV vaccine on an off-label basis before 2009. This study utilized administrative claims data from a private insurance company to examine completion of the 3 dose HPV series among 514 males who initiated the vaccine between 2006 and May of 2009. Frequencies of HPV vaccination were examined and multivariate logistic regression estimated the odds of completing the entire series within 365 days of initiation. We found that only 21% of male initiators completed all 3 vaccine doses within 12 months and completion decreased over time. Series completion did not vary significantly by provider type. These findings suggest that difficulties may be encountered in fully vaccinating enough males to achieve adequate herd immunity in the future.     

The cost-effectiveness of male HPV vaccination in the United States

Introduction

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States.

Methods

We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers.

Results

The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated.

Conclusions

HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population.     

A qualitative study investigating knowledge and attitudes regarding human papillomavirus (HPV) and the HPV vaccine among parents of immunosuppressed children

Barriers influencing the willingness of parents to vaccinate immunocompetent children include a lack of knowledge about human papillomavirus (HPV) and low perception of risk regarding their child's acquisition of HPV infection. However, it cannot be assumed that the facilitators and barriers of HPV vaccination are the same for parents/guardians of children who are immunocompromised, or who have chronic medical conditions. This study aimed to document the knowledge and attitudes of parents/guardians of immunosuppressed children and adolescents towards HPV infection and the vaccine.     

16～26岁女性接种人乳头瘤病毒疫苗的经济性研究

目的 从卫生体系角度评价接种2、4、9价人乳头瘤病毒(Human Papilloma Virus, HPV)疫苗相比不接种疫苗的经济性。方法 构建静态模型并嵌入宫颈癌马尔可夫模型,模拟16～26岁女性未来60年的健康状态与成本消耗,两两比较增量成本效果比(Increased cost-effectiveness ratio, ICER),并计算意愿支付阈值(Willingness to pay, WTP)下的净效益,判断经济性。结果 基础分析显示接种2、4、9价HPV疫苗相对于不接种疫苗的ICER分别为2 281.2元/QALY、22 878.07元/QALY和45 497.56元/QALY,净效益分别为1 298.15元、1 079.84元和593.57元; 接种4价疫苗相对于接种2价疫苗的ICER为139 756.95元/QALY,净效益为251.64元; 9价疫苗相较于2、4价疫苗的ICER值分别为272 399.41元/QALY和1 807 163.88元/QALY。单因素敏感性显示,是否接种疫苗与4价、2价疫苗的对比中,参数变化不会导致ICER值超过经济性阈值。概率敏感性分析显示,当WTP为72 447元/QALY时,接种2价疫苗的经济性概率为98.8%; 当WTP为217 341元/QALY时,接种4价疫苗的经济性概率为94.8%。结论 从卫生体系角度看,在1倍人均GDP的WTP下,接种2、4、9价HPV疫苗均具有经济性,在3倍人均GDP的WTP下,接种4价疫苗最具有经济性。     

Factors associated with human papillomavirus vaccination among young adult women in the United States

Background

Human papillomavirus (HPV) vaccination is recommended to protect against HPV-related diseases.

Objective

To estimate HPV vaccine coverage and assess factors associated with vaccine awareness, initiation and receipt of 3 doses among women age 18–30 years.

Methods

Data from the 2010 National Health Interview Survey were analyzed to assess associations of HPV vaccination among women age 18–26 (n = 1866) and 27–30 years (n = 1028) with previous HPV exposure, cervical cancer screening and selected demographic, health care and behavioral characteristics using bivariate analysis and multivariable logistic regression.

Results

Overall, 23.2% of women age 18–26 and 6.7% of women age 27–30 years reported receiving at least 1 dose of HPV vaccine. In multivariable analyses among women age 18–26 years, not being married, having a regular physician, seeing a physician or obstetrician/gynecologist in the past year, influenza vaccination in the past year, and receipt of other recommended vaccines were associated with HPV vaccination. One-third of unvaccinated women age 18–26 years (n = 490) were interested in receiving HPV vaccine. Among women who were not interested in receiving HPV vaccine (n = 920), the main reasons reported included: not needing the vaccine (41.3%); concerns about safety of the vaccine (12.5%); not knowing enough about the vaccine (11.9%); not being sexually active (8.2%); a doctor not recommending the vaccine (7.6%); and already having HPV (2.7%). Among women with health insurance, 10 or more physician contacts within the past year and no contraindications, 74.5% reported not receiving HPV vaccine.

Conclusions

HPV vaccination coverage among women age 18–26 years remains low. Opportunities to vaccinate are missed. Healthcare providers can play an important role in educating young women about HPV and encouraging vaccination. Successful public health and educational interventions will need to address physician attitudes and practice patterns and other factors that influence vaccination behaviors.     

Preparing for HPV vaccination in South Africa: key challenges and opinions

This article reports on qualitative research investigating key challenges and barriers towards human papillomavirus (HPV) vaccine introduction in the Western Cape Province, South Africa. A total of 50 in-depth interviews and 6 focus groups were conducted at policy, health service and community levels of enquiry. Respondents expressed overall support for the HPV vaccine, underscored by difficulties associated with the current cervical screening programmes and the burgeoning HIV/AIDS epidemic in South Africa. Overall poor community knowledge of cervical cancer and the causal relationship between HPV and cervical cancer suggests the need for continued education around the importance of regular cervical screening. The optimal target populations for HPV vaccination was influenced by the perceived median age of sexual activity in South African girls (9-15 years), with an underlying concern that high levels of sexual abuse had significantly decreased the age of sexual exposure suggesting vaccination should commence as early as 9 years. Vaccination through schools with the involvement of other stakeholders such as sexual and reproductive health and the advanced programme on immunization (EPI) were suggested. Opposition to the HPV vaccine was not anticipated if the vaccine was marketed as preventing cervical cancer rather than a sexually transmitted infection. The findings assist in identifying potential barriers and facilitating factors towards HPV vaccines and will inform the development of policy and programs to support HPV vaccination introduction in South Africa and other African countries.     

Female human papillomavirus (HPV) vaccination: Global uptake and the impact of attitudes

Human papillomavirus (HPV) is the causative agent in cervical cancer and has been implicated in a range of other malignancies. Preventative vaccines are now internationally available and provide high levels of protection from common viral strains. The introduction of a comprehensive vaccination programme (except ‘program’ in computers) could prevent over 60% of current cervical cancer cases, but this is dependent on such programmes achieving a high level of coverage. In this review, we summarise the current trends in female HPV vaccination coverage throughout the world, and place it in the context of available research on attitudes towards vaccination amongst the public and health professionals.     

Evaluating the impact of human papillomavirus vaccines

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.     

Safety of human papillomavirus (HPV) vaccines: A review of the international experience so far

Despite the advent of the Papanicolaou smear test almost 50 years ago, cervical cancer remains the second most common malignant disease in women and the leading cause of cancer death in developing countries. Thus the two prophylactic human papillomavirus (HPV) vaccines currently available have been greeted with enthusiasm internationally, as an emerging primary prevention strategy against cervical cancer. Prior to licensure the vaccines were trialed in over 60,000 women and assessed as safe, within the statistical constraints of the trials to detect very rare events. Post-licensure surveillance is underway as vaccination programs are undertaken. We reviewed published post-licensure surveillance data, as at January 2009, and concur with international advisory bodies that both HPV vaccines are safe, effective and of great importance for women's health. Ongoing monitoring is required to maintain confidence in the safety of the vaccines.