Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-Valent vaccine,gender-neutral and multiple age cohort vaccination

BackgroundThe success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.MethodsSearches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.ResultsThirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9–14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.ConclusionsThese findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys’ vaccination or extending the age of vaccination.     

A systematic review of measures used in studies of human papillomavirus (HPV) vaccine acceptability

Background

The recent proliferation of studies describing factors associated with HPV vaccine acceptability could inform health care providers in improving vaccine coverage and support future research. This review examined measures of HPV and HPV-vaccine knowledge, attitudes, beliefs and acceptability, described psychometric characteristics, and provided recommendations about their use.

Methods

A systematic search of Medline, CINAHL, PsychoInfo, and ERIC through May 2008 for English language reports of quantitative data from parents, young adults or adolescents yielded 79 studies.

Results

The majority of studies were cross-sectional surveys (87%), self-administered (67%), conducted before prophylactic vaccines were publicly available (67%) and utilized convenience samples (65%). Most measured knowledge (80%), general attitudes about HPV vaccination (40%), and willingness to vaccinate one's daughter (26%). Two-thirds did not report reliability or validity of measures. The majority did not specify a theoretical framework.

Conclusions

Use of a theoretical framework, consistent labeling of constructs, more rigorous validation of measures, and testing of measures in more diverse samples are needed to yield measurement instruments that will produce findings to guide practitioners in developing successful community and clinical interventions.     

人类乳头瘤病毒疫苗保护效果Meta分析

目的 评价人类乳头瘤病毒(HPV)疫苗流行病学保护效果.方法 电子检索National Center for Biotechnology Information(NCBI)(《美国国家医学图书馆数据库》)、《Cochrane协作网图书馆》等数据库,将有关接种HPV流行病学保护效果的研究文献进行分析.文献资料使用RevMan5.1软件进行meta分析.结果 符合标准的文献共10篇,均为随机对照试验(RCT).HPV疫苗对相关基因型人类乳头瘤病毒(HPV)引起的尖锐湿疣的疫苗保护效果(VE)为94％(95％ CI:91％～96％),对外阴上皮内瘤样病变Ⅱ/Ⅲ级(VIN2/3)和阴道上皮内瘤样病变(VaIN)的VE为96％(95％CI:86％～99％),对宫颈上皮内瘤样病变Ⅱ/Ⅲ级(CIN2/3),原位癌(AIS)的VE分别为98％(95％ CI:96％-99％)和79％(95％Cl:55％-90％).结论 接种HPV疫苗可以降低尖锐湿疣、VIN2/3、VaIN、CIN2/3和AIS的发病率,具有良好的保护效果.     

Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis

BackgroundHuman papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes.MethodsWe performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes.ResultsOf 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78–91%) was higher than that for the quadrivalent vaccine (61%; 39–79%; p = 0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37–64%) was also higher than that for the quadrivalent vaccine (16%; 6–36%; p = 0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials.ConclusionsThese data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting.     

人乳头瘤病毒疫苗安全性研究的新进展

人乳头瘤病毒(HPV)的持续感染是导致子宫颈癌的主要致病因素,全球每年约63万例新发癌症由HPV感染所致,其中子宫颈癌占比最高,达83%。中国子宫颈癌的疾病负担严重,研究数据显示,2018年中国子宫颈癌新发病例近11万,死亡病例近5万,分别约占全球发病和死亡总数的20%和16%。世界卫生组织(WHO)的立场文件中明确指出,HPV疫苗的接种可有效预防HPV相关疾病的发生。纵观全球的临床研究及真实世界数据,HPV疫苗显示出良好的保护效力及安全性。截至2019年10月,全球已有98个国家和地区将HPV疫苗纳入国家免疫计划。然而,伴随接种范围的增加及适应证的扩大,HPV疫苗的安全性成为了全球高度关注的公共卫生问题。自2006年HPV疫苗上市以来,各国多家权威机构均对HPV疫苗上市后的安全性进行长期监测,积累了大量的安全性数据,数据显示HPV疫苗安全性良好并支持HPV疫苗的使用。本文将针对全球及中国大陆的HPV疫苗相关的安全性数据进行梳理,为中国HPV疫苗的接种提供参考。     

Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis

BackgroundUnderstanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States.MethodsWe searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089).ResultsOf 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of  intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE).ConclusionsAcross a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide.     

Acceptability of the human papillomavirus vaccine and reasons for non-vaccination among parents of adolescent sons

Routine administration of the quadrivalent human papillomavirus (HPV) vaccine has been recommended for 11–12-year-old males since 2011, but coverage remains low. In a U.S. national sample of parents of 11–17-year-old males (n = 779), 78.6% of parents reported their sons had not received the HPV vaccine. The most common reason for non-vaccination (56.7%) was “My doctor or healthcare provider has not recommended it.” Parents citing only logistical reasons for non-vaccination (e.g., lack of recommendation, access, or education, n = 384) reported significantly higher vaccine acceptability than parents reporting a combination of attitudinal (e.g., concerns about vaccine safety or efficacy) and logistical barriers (n = 92), while parents citing only attitudinal barriers (n = 73) reported the lowest level of vaccine acceptability. In sum, many parents are willing but have not vaccinated sons due to logistical barriers, most commonly lack of healthcare provider recommendation. These findings have important implications for increasing HPV vaccination coverage among adolescent males.     

Comparing pneumococcal conjugate vaccine schedules based on 3 and 2 primary doses: systematic review and meta-analysis

Background

Pneumococcal conjugate vaccines (PCV) were first licensed for use with 3 primary doses in infancy and a booster dose. The evidence for the effects of different schedules was examined in this systematic review and meta-analysis.

Methods

We searched 12 databases and trial registers up to March 2010. We selected randomised controlled trials (RCTs), cohort and case-control studies making direct comparisons between PCV schedules with (2p) or (3p) primary doses, with (+1) or without (+0) a booster dose. We extracted data on clinical, nasopharyngeal carriage and immunological outcomes and used meta-analysis to combine results where appropriate.

Results

Seropositivity levels (antibody concentration ≥0.35 μg/ml) following 3p and 2p PCV schedules were high for most serotypes (5 RCTs). Differences between schedules were generally small and tended to favour 3p schedules, particularly for serotypes 6B and 23F; between-study heterogeneity was high. Seropositivity levels following 3p+1 and 2p+1 schedules were similar but small differences favouring 3p+1 schedules were seen for serotypes 6B and 23F. We did not identify any RCTs reporting clinical outcomes for these comparisons. In 2 RCTs there was weak evidence of a reduction in carriage of S. pneumoniae serotypes included in the vaccine when 3p+0 schedules were compared to 2p+0 at 6 months of age.

Conclusions

Most data about the relative effects of different PCV schedules relate to immunological outcomes. Both 3p and 2p schedules result in high levels of seropositivity. The clinical relevance of differences in immunological outcomes between schedules is not known. There is an absence of clinical outcome data from RCTs with direct comparisons of any 2p with any 3p PCV schedule.     

Influenza vaccine effectiveness against influenza-associated hospitalization in children: A systematic review and meta-analysis

Vaccination remains the most effective way to prevent influenza infection, albeit vaccine effectiveness (VE) varies by year. Compared to other age groups, children and elderly adults have the highest risk of developing influenza-related complications and requiring hospitalization. During the last years, “test negative design” (TND) studies have been implemented in order to estimate influenza VE. The aim of this systematic review and meta-analysis was to summarize the findings of TND studies reporting influenza VE against laboratory-confirmed influenza-related hospitalization in children aged 6 months to 17 years. We searched the PubMed and Embase databases and identified 2615 non-duplicate studies that required detailed review. Among them, 28 met our inclusion criteria and we performed a random-effects meta-analysis using adjusted VE estimates. In our primary analysis, influenza vaccine offered significant protection against any type influenza-related hospitalization (57.48%; 95% CI 49.46–65.49). When we examined influenza VE per type and strain, VE was higher against H1N1 (74.07%; 95% CI: 54.85–93.30) and influenza B (50.87%; 95% CI: 41.75–59.98), and moderate against H3N2 (40.77%; 95% CI: 25.65–55.89). Notably, influenza vaccination offered higher protection in children who were fully vaccinated (61.79%; 95% CI: 54.45–69.13), compared to those who were partially vaccinated (33.91%; 95% CI: 21.12 – 46.69). Also, influenza VE was high in children less than 5 years old (61.71%; 95% CI: 49.29–74.12) as well as in children 6–17 years old (54.37%; 95% CI: 35.14–73.60). In conclusion, in the pediatric population, influenza vaccination offered significant protection against influenza-related hospitalization and complete annual vaccination should be encouraged.     

Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis

IntroductionOlder adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age > 65).MethodsData sources: Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray literature.Study selection: Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60 μg of hemagglutinin per strain) to standard-dose influenza vaccine (15 μg of hemagglutinin per strain) in adults over the age of 65 years.Data extraction: Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool.ResultsWe included seven eligible trials; all were categorized as having a low (n = 3) or unclear (n = 4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory-confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I² 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group.ConclusionsIn elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65.     

Factors associated with HPV vaccine uptake in teenage girls: a systematic review

Background

Since 2006 Human papillomavirus (HPV) vaccination has become available to adolescent girls and women in an increasing number of countries, to protect against the virus causing cervical cancer. The vaccine series is offered in three doses over 6 months, and this study aimed to identify factors associated with initiation and/or completion of the 3 dose series in (pre-) adolescent girls. Previous studies have considered intention to vaccinate rather than actual vaccination uptake.

Methods

A systematic search of Medline, Medline in process, Embase and CINAHL, from 2006 to March 2011 for articles related to HPV-vaccine uptake among adolescent girls and factors potentially associated with uptake yielded 25 studies.

Results

The majority of studies were surveys or retrospective reviews of data, only 5 studies reported data on program completion. Most were conducted in the United States (20/25). Higher vaccine uptake was associated with having health insurance, of older age, receipt of childhood vaccines, a higher vaccine related knowledge, more healthcare utilization, having a healthcare provider as a source of information and positive vaccine attitudes. In US settings, African American girls were less likely to have either initiated or completed the three dose vaccination series.

Conclusions

HPV vaccination programs should focus on narrowing disparities in vaccine receipt in ethnic and racial groups and on providing correct information by a reliable source, e.g. healthcare providers. School-based vaccination programs have a high vaccine uptake. More studies are required to determine actual vaccine course completion and factors related to high uptake and completion, and information from a broader range of developed and developing settings is needed.     

Determinants of the receipt of the 9-valent human papillomavirus vaccine in the first year after introduction in North Carolina

ObjectivesThe objective of this study was to describe the transition from bi- and quadrivalent HPV vaccines to 9vHPV in aggregate and identify determinants of the receipt of 9vHPV among youth following the introduction of 9vHPV in North Carolina.MethodsThe study used a retrospective cohort design with data from the North Carolina Immunization Registry (NCIR). Our sample included all doses of HPV vaccine administered between July 2015 and October 2016 to age-eligible youth (ages 9–17). We used a logistic regression model to associate individual child-level and ZIP Code Tabulation Area (ZCTA)-level characteristics with an indicator variable for receiving 9vHPV (vs. other HPV vaccines).ResultsYouth receiving the HPV vaccine were more likely to receive 9vHPV if they lived in a ZCTA with a larger age-eligible (i.e., 9–17) population, a health professional shortage area, or a higher number of annual outpatient visits per capita. They were less likely to receive 9vHPV if they were older, received a publicly-funded dose, or lived in a ZCTA with a higher percentage of the population with less than a high-school education or a higher number of religious organizations.ConclusionsWhile the transition from other HPV vaccines to 9vHPV was relatively quick, there were disparities in the diffusion of 9vHPV across North Carolina.     

Incident autoimmune conditions among males receiving quadrivalent human papillomavirus vaccine in the United States

BackgroundThe potential for vaccines to induce autoimmunity has been the subject of considerable investigation and autoimmune induction remains a common focus for vaccine safety research. This study assessed the risk of new onset autoimmune conditions among males receiving the 4-valent human papillomavirus (HPV) vaccine (4vHPV).MethodsWithin a US health insurance claims database, we formed a cohort of male 4vHPV vaccine recipients between 2009 and 2016, along with a propensity score matched cohort of males who did not receive the 4vHPV vaccine. The study outcome was new onset autoimmune conditions (20 separate conditions) within four categories (rheumatologic/hematologic, gastroenterologic, endocrinologic and neurologic/ophthalmalogic). Outcomes identified using diagnosis codes were adjudicated through medical record review. Incidence rates (per 1,000 person-years) were estimated for the vaccinated and unvaccinated groups along with rate ratios (RRs).ResultsThere were 65,606 males receiving at least one dose of 4vHPV vaccine, and 55,670 were matched to a comparator. The matched 4vHPV vaccine cohort provided 35 confirmed cases among 39,735 person-years, for an incidence rate of 0.88 (95% CI: 0.61–1.23), while the comparator cohort provided 47 confirmed cases among 58,215 person-years, an incidence rate of 0.81 (0.59–1.07), a RR of 1.09 (0.70–1.69). The RR within categories was 0.49 (0.10–2.42) for rheumatologic/hematologic, 1.26 (0.58–2.71) for gastroenterologic, 1.11 (0.61–2.02) for endocrinologic and 1.46 (0.21–10.40) for neurologic.ConclusionsThe incidence of autoimmune conditions among males receiving the 4vHPV vaccine was similar to that among unvaccinated males. These results are consistent with other studies that have assessed autoimmunity with the 4vHPV vaccine.     

Patient and clinic factors associated with adolescent human papillomavirus vaccine utilization within a university-based health system

We reviewed clinical and billing data from a university-based health system to assess HPV vaccine utilization among 9–18-year-old girls by individual, visit and medical specialty characteristics. Our sample included 10,082 adolescent patients with 27,928 visits to outpatient family medicine (FM), pediatric and gynecology clinics between January 2007 and March 2008. Vaccine series completion was low among eligible adolescents (15%), with important disparities in vaccine utilization by medical specialty, age, race and insurance status. Missed opportunities for vaccination were common. Our findings may help to target future interventions aimed at increasing adolescent HPV vaccine utilization.     

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.     

Determinants for HPV vaccine uptake in the Netherlands: A multilevel study

In March 2009, a HPV catch-up vaccination campaign was implemented in the Netherlands for girls born between 1993 and 1996. We performed a multilevel study to investigate determinants for HPV vaccination uptake. National coverage for the first dose was 49.9%, with regional uptakes ranging from 31% to 61%. Data was gathered from individual to regional level. Our results suggest that organizing information meetings at schools and communicating with gynaecologists might be beneficial. Lower uptake among various ethnic groups and in areas with higher proportion of voters for Religious Political Parties indicate that communication on HPV vaccine should be adapted to religious and ethnic communities. Furthermore, lower uptake in areas with lower socioeconomic status needs attention since participation to cervical screening is also lower in these areas.     

Human papillomavirus vaccination coverage,policies, and practical implementation across Europe

BackgroundOur objectives were to describe Human Papillomavirus vaccination coverage rates (HPV-VCR), policies, and practical steps for programme implementation that may be linked to high uptake in the population targeted by routine programmes across 30 European Union/European Economic Area Member States and Switzerland.MethodsInformation from institutional websites and from articles indexed in Medline between 01/2006 and 01/2017 was reviewed and extracted using a standardised form. In 12/2017, a cross-sectional survey was administered to national experts, in order to update the compiled information.ResultsData were available in 31 countries, and validated by national experts in 28 of them. National vaccination programmes targeted girls 9–15 years of age in 30 countries and boys in 11 countries. HPV-VCR in girls was monitored in 25 countries: VCR was reported ≥71%(high) in ten countries, 51–70% in seven, 31–50% in four, and ≤30%(very low) in four. In high VCR countries, HPV vaccination was mainly delivered through school health services, and invitation and reminders to attend for vaccination were used. In areas with very low VCR, vaccination tended to be opportunistic and no reminders were used.ConclusionAccording to our findings, school delivery within structured vaccination programmes and the use of reminders tended to be associated with highest HPV-VCR.     

The study of human papillomavirus (HPV) vaccine uptake from a parental perspective: a systematic review of observational studies in the United States

Despite widespread information about the human papillomavirus (HPV) vaccine, uptake continues to be low (CDC, 2010). HPV vaccine uptake may be maximized by better understanding factors likely to influence parents' decisions to vaccinate their age-recommended children. Previous reviews have summarized barriers and facilitators likely to influence parents' decision to vaccinate their adolescents (mostly daughters) against HPV; however, less attention has been given to summarize and evaluate the methodology. The aim of this study is to systematically review the methodology used in observational studies of HPV vaccine uptake from a parental perspective. A systematic search of Academic Search Premier, CINAHL, ERIC, Medline and PsycInfo to obtain relevant articles after FDA vaccine approval (2006 to present) yielded 446 studies, of which 17 studies were eligible. Results showed the majority of studies were cross-sectional, with random sampling from list-assisted sources being the most common method for data collection. Most studies used convenience samples and relied on parental self-report. Also, the majority of studies explored vaccine initiation, but only a few explored regimen completion and timely completion of vaccine regimen. Given that the effectiveness of the HPV vaccine is based on established recommendations for a three dose regimen within a timely interval, studies on factors likely to influence regimen completion and timely completion of regimen are essential to maximize the effectiveness and public health benefits of the vaccine. Research with more diverse samples, better and increased use of random sampling techniques, and the use of precise and objective measures of vaccine uptake to supplement parental self-report, is necessary to reduce selection and information biases in future studies. Studies to inform on factors likely to influence parents' decisions to vaccinate their sons against HPV are also needed.     

Longer term efficacy of a prophylactic monovalent human papillomavirus type 16 vaccine

We conducted an extended follow-up study (March 2006–May 2008) to assess the longer term efficacy of a prophylactic monovalent human papillomavirus (HPV) type 16 L1 virus-like particle vaccine in women (n = 290) who had enrolled in a randomized controlled trial of this vaccine (October 1998–November 1999) in Seattle and remained HPV-16 DNA negative during the course of that trial. During the extended follow-up period, in the per-protocol susceptible population, none of the vaccine recipients was found to be infected with HPV-16 or developed HPV-16-related cervical lesions; among placebo recipients, 6 women were found to be infected with HPV-16 (vaccine efficacy [VE] = 100%; 95% confidence interval [CI]: 29–100%) and 3 women developed HPV-16-related cervical lesions (VE = 100%; 95% CI: <0–100%). Approximately 86% of vaccine recipients remained HPV-16 competitive Luminex immunoassay seropositive at an average of 8.5 years of follow-up. During the combined original trial and extended follow-up period, in the intention-to-treat population, 20 and 22 women developed any cervical lesion regardless of HPV type among the vaccine and placebo recipients, respectively (VE = 15%; 95% CI: <0–56%). The results suggest that this monovalent HPV-16 vaccine remains efficacious through 8.5 years after its administration.     

Differences between vaccinated and unvaccinated women explain increase in non-vaccine-type human papillomavirus in unvaccinated women after vaccine introduction

The aim of this study was to determine whether an observed increase in non-vaccine-type human papillomavirus (HPV) in unvaccinated women during the first eight years after vaccine introduction may be explained by differences in demographics or sexual behaviors, instead of type replacement. We analyzed data from three cross-sectional surveillance studies of 13–26 year-old women (total N = 1180). For women recruited from a health department clinic, older age (OR = 1.4, 95% CI: 1.2–1.6) and consistent condom use with main partner in the past 3 months (OR = 11.6, 95% CI: 3.4–40) were associated with being unvaccinated. For women recruited from a teen health center African American race (OR = 0.2, 95% CI: 0.07–0.7) and having Medicaid health insurance (OR = 0.3, 95% CI: 0.1–0.7) were inversely associated with being unvaccinated. The observed increase in non-vaccine-type HPV prevalence in unvaccinated women may be explained by differences between unvaccinated and vaccinated women.