In 2006, human papillomavirus (HPV) vaccine was first recommended in the United States to prevent cancers and other diseases caused by HPV; vaccination coverage increased steadily through 2021, and increasing numbers of young women had received HPV vaccine as children or adolescents. Since 2008, CDC has monitored incidence of precancerous lesions (cervical intraepithelial neoplasia [CIN] grades 2-3 and adenocarcinoma in situ [AIS], collectively CIN2+), which are detected through cervical cancer screening and can be used as an intermediate outcome for monitoring vaccination impact, via the five-site Human Papillomavirus Vaccine Impact Monitoring Project. This analysis describes trends in incidence of CIN2+ and CIN3+ (i.e., CIN grade 3 and AIS) lesions during 2008-2022. Among women aged 20-24 years who were screened for cervical cancer, rates during 2008-2022 decreased for CIN2+ by 79%, and for CIN3+ by 80%. In the same period, CIN3+ rates among screened women aged 25-29 years decreased by 37%. These data are consistent with considerable impact of HPV vaccination for preventing cervical precancers among women in the age groups most likely to have been vaccinated, and support existing recommendations to vaccinate children at the routinely recommended ages as a cancer prevention measure.

Objectives: Although invasive cervical cancer (ICC) rates have declined since the advent of screening, the annual age-adjusted ICC rate in the United States remains 7.5 per 100,000 women. Failure of recommended screening and management often precedes ICC diagnoses. The study aimed to evaluate characteristics of women with incident ICC, including potential barriers to accessing preventive care. Materials and Methods: We abstracted medical records for patients with ICC identified during 2008-2020 in five U.S. population-based surveillance sites covering 1.5 million women. We identified evidence of adverse social and medical conditions, including uninsured/underinsured, language barrier, substance use disorder, incarceration, serious mental illness, severe obesity, or pregnancy at diagnosis. We calculated descriptive frequencies and compared potential barriers by race/ethnicity, and among women with and without symptoms at diagnosis using chi-square tests. Results: Among 1,606 women with ICC (median age: 49 years; non-White: 47.4%; stage I: 54.7%), the majority (68.8%) presented with symptoms. Forty-six percent of women had at least one identified potential barrier; 15% had multiple barriers. The most common potential barriers among all women were being underinsured/uninsured (17.3%), and language (17.1%). Presence of any potential barrier was more frequent among non-White women and women with than without symptoms (p < 0.05). Conclusions: In this population-based descriptive study of women with ICC, we identified adverse circumstances that might have prevented women from seeking screening and treatment to prevent cancer. Interventions to increase appropriate cervical cancer screening and management are critical for reducing cervical cancer rates.

Human papillomavirus (HPV) causes cervical as well as other cancers. Racial and ethnic disparities in cervical cancer incidence and mortality in the United States are well documented. HPV vaccination has been recommended in the United States since 2006 and is expected to prevent HPV-attributable cancers in all racial/ethnic groups. Quadrivalent HPV vaccine-type (HPV6/11/16/18) and nonvaccine-type cervicovaginal HPV prevalences were estimated from National Health and Nutrition Examination Surveys in 2015-2018 (vaccine era) and 2003-2006 (prevaccine era) data. Prevalence ratios comparing 2015-2018 to 2003-2006 were calculated among sexually experienced Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Mexican American (MA) females aged 14-24 years. Quadrivalent HPV vaccine-type prevalence declined 82% (CI: 60%-92%) among NHW, 86% (CI: 64%-95%) among NHB, and 100% among MA females, forecasting future reductions in cervical cancer across racial/ethnic groups.

To inform Advisory Committee for Immunization Practices (ACIP) COVID-19 vaccine policy decisions, we developed a benefit-risk assessment framework that directly compared the estimated benefits of COVID-19 vaccination to individuals (e.g., prevention of COVID-19-associated hospitalization) with risks associated with COVID-19 vaccines. This assessment framework originated following the identification of thrombosis with thrombocytopenia syndrome (TTS) after Janssen COVID-19 vaccination in April 2021. We adapted the benefit-risk assessment framework for use in subsequent policy decisions, including the adverse events of myocarditis and Guillain-Barre syndrome (GBS) following mRNA and Janssen COVID-19 vaccination respectively, expansion of COVID-19 vaccine approvals or authorizations to new age groups, and use of booster doses. Over the first year of COVID-19 vaccine administration in the United States (December 2020-December 2021), we used the benefit-risk assessment framework to inform seven different ACIP policy decisions. This framework allowed for rapid and direct comparison of the benefits and potential harms of vaccination, which may be helpful in informing other vaccine policy decisions. The assessments were a useful tool for decision-making but required reliable and granular data to stratify analyses and appropriately focus on populations most at risk for a specific adverse event. Additionally, careful decision-making was needed on parameters for data inputs. Sensitivity analyses were used where data were limited or uncertain; adjustments in the methodology were made over time to ensure the assessments remained relevant and applicable to the policy questions under consideration.

We were pleased to receive the response from Escobedo, et al to our recent manuscript describing giardiasis diagnosis and treatment patterns in the United States. They shared a summary of similar diagnosis and treatment patterns among giardiasis patients in Cuba, notably, that diagnoses are often delayed. They offer a framework for understanding and addressing these patterns based on surveys conducted among Cuban patients, caregivers and physicians. We wish to thank them for their insights, and highlight opportunities for US clinical and public health professionals to explore and address factors underlying delayed diagnoses and ineffective treatment in this country.

In December 2020, an interim recommendation for the use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years was made under Food and Drug Administration's Emergency Use Authorization. In preparation for Biologics License Application approval, we conducted a systematic review and meta-analysis to inform the U.S. Centers for Disease Control and Prevention's Advisory Committee for Immunization Practice's (ACIP) decision-making for a standard recommendation. We conducted a rapid systematic review and meta-analysis of Pfizer-BioNTech vaccine effectiveness (VE) against symptomatic COVID-19, hospitalization due to COVID-19, death due to COVID-19, and asymptomatic SARS-CoV-2 infection. We identified studies through August 20, 2021 from an ongoing systematic review conducted by the International Vaccine Access Center and the World Health Organization. We evaluated each study for risk of bias using the Newcastle-Ottawa Scale. Pooled estimates were calculated using meta-analysis. The body of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We identified 80 articles, selected 35 for full-text review, and included 26. The pooled VE of Pfizer-BioNTech COVID-19 vaccine was 92.4% (95% CI: 87.5%-95.3%) against symptomatic COVID-19 with moderate evidence certainty (eight studies), 94.3% (95% CI: 87.9%-97.3%) against hospitalization due to COVID-19 with moderate certainty (eight studies), 96.1% (95% CI: 91.5%-98.2%) against death due to COVID-19 with moderate certainty (four studies), and 89.3% (88.4%-90.1%) against asymptomatic SARS-CoV-2 infection with very low certainty (two studies). The Pfizer-BioNTech COVID-19 vaccine demonstrated high effectiveness in all pre-specified outcomes and extended knowledge of the vaccine's benefits to outcomes and populations not informed by the RCTs. Use of an existing systematic review facilitated a rapid meta-analysis to inform an ACIP policy decision. This approach can be utilized as additional COVID-19 vaccines are considered for standard recommendations by ACIP.

Declines in cervical intraepithelial neoplasia grades 2-3 and adenocarcinoma in situ (CIN2+) observed among young women suggest impact from human papillomavirus (HPV) vaccination. To further evaluate vaccine impact including cross-protection and type replacement, we described high-risk (HR)-HPV type-specific cervical precancer incidence rates among women aged 20-39 years, 2008-2016. We analyzed cross-sectional population-based data on 18,344 cases of CIN2+ from a 5-site surveillance system. Diagnostic specimens were tested for individual HPV types, including 14 HR-HPV types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68). We estimated age-specific annual HR-HPV type-specific CIN2+ incidence per 100,000 screened women for individual types, vaccine HR-HPV types (HPV16/18) and non-vaccine HR-HPV types (non-HPV16/18). We evaluated trends using average annual percent changes (AAPC) and 95% confidence intervals (CI), and estimated total declines by comparing 2015-2016 to 2008-2009 using incidence rate ratios. Among 20-24-year-olds, HPV16/18-CIN2+ declined from 2008 through 2016 (AAPC: -21.3%, 95% CI: -28.1%, -13.8%), whereas no trend was observed for non-HPV16/18-CIN2+ (AAPC: -1.8%, 95% CI: -8.1%, 4.9%). After 2010, CIN2+ among 20-24-year-olds was more often caused by non-vaccine versus vaccine HR-HPV types. No significant declining trends were observed in older age groups. In 2015-2016 compared to 2008-2009, HPV16-CIN2+ declined 78%, HPV18-CIN2+ 72%, and HPV31-CIN2+ 51% among 20-24-year-olds; no increases were observed in type-specific CIN2+ incidence. Among 25-29-year-olds, HPV16-CIN2+ declined 18%; CIN2+ attributed to seven nonvaccine types increased significantly. No significant declines were observed in older groups. Significant declines in HPV16/18-CIN2+ in 20-24-year-olds and HPV16-CIN2+ in 25-29-year-olds corroborate impact of HPV vaccination. A declining trend in HPV31-CIN2+ is consistent with cross-protection from vaccination.

BACKGROUND: Human papillomavirus (HPV) vaccination was introduced in 2006 for females and in 2011 for males. OBJECTIVE: To estimate vaccine impact and effectiveness against quadrivalent HPV vaccine (4vHPV)-type prevalent infection among sexually experienced U.S. females and vaccine effectiveness for sexually experienced U.S. males. DESIGN: NHANES (National Health and Nutrition Examination Survey) conducted in 2003 to 2006 (prevaccine era) and in 2007 to 2010, 2011 to 2014, and 2015 to 2018 (vaccine eras). SETTING: Nationally representative U.S. surveys. PARTICIPANTS: Sexually experienced participants aged 14 to 24 years. INTERVENTION: U.S. HPV vaccination program. MEASUREMENTS: Participant-collected cervicovaginal and penile specimens were tested for HPV DNA. The prevalences of 4vHPV and non-4vHPV types were estimated in each era for females and in 2013 to 2016 for males. Prevalences among the female population overall, vaccinated females, and unvaccinated females were compared in vaccine eras versus the prevaccine era (vaccine impact). Within each vaccine era, prevalence among vaccinated females was compared with that among unvaccinated females (vaccine effectiveness). Vaccine impact and effectiveness were estimated as (1 - prevalence ratio) · 100. RESULTS: Among sexually experienced females aged 14 to 24 years, the impact on 4vHPV-type prevalence in 2015 to 2018 was 85% overall, 90% among vaccinated females, and 74% among unvaccinated females. No significant declines were found in non-4vHPV-type prevalence. Vaccine effectiveness ranged from 60% to 84% during vaccine eras for females and was 51% during 2013 to 2016 for males. LIMITATION: Self- or parent-reported vaccination history and small numbers in certain subgroups limited precision. CONCLUSION: Nationally representative data show increasing impact of the vaccination program and herd protection. Vaccine effectiveness estimates will be increasingly affected by herd effects. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

In 2015, Botswana introduced the quadrivalent human papillomavirus (HPV) vaccine as a two-dose schedule in girls aged 9-13 years. We sought to establish a baseline HPV prevalence in unvaccinated young adults in Botswana. HIV-uninfected men and women aged 18-22 years were recruited from the University of Botswana in Gaborone during October 2019-February 2021. Demographic and behavioural characteristics were self-reported during structured interviews. Self-collected vaginal and penile swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared any HPV type, quadrivalent vaccine (HPV 6, 11, 16, 18)-type and non-quadrivalent vaccine-type prevalence in men and women and evaluated the risk factors for prevalence of any HPV type. A total of 493 men and 500 women were included in the analysis. Compared to men, women had higher prevalence of any HPV type (63.0% versus 31.4%, P < 0.001), vaccine-type HPV (21% versus 9.7%, P < 0.001) and non-vaccine-type HPV (60.4% versus 28.4%, P < 0.001). Higher prevalence of any HPV type in men and women was associated with having >/=2 sex partners in the past 12 months; always using condoms in the past 3 months was associated with a lower HPV prevalence. These data provide baseline information for future evaluation of the population impact of the HPV vaccination programme, including potential herd effects in men.

BACKGROUND: Racial and ethnic variations in attribution of cervical precancer and cancer to HPV types may result in different HPV vaccine protection, screening test coverage, and clinical management. METHODS: Pooling data from seven U.S. studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. RESULTS: For all racial and ethnic groups, most cervical intraepithelial neoplasia grade 3 (CIN3) (n=5,526) and squamous cell carcinoma (SCC) cases (n=1,138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to non-vaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%, P=.002), non-Hispanic White (9.2%, P<.001), and Hispanic women (11.3%, P=.004). The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (90.4%-93.8%, P=.80). A higher proportion of CIN3s were attributed to non-vaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic women (3.0%, all P<.001). Compared with CIN3, the proportion of SCCs attributed to HPV35 among Non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%, P=.70). CONCLUSION: The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35 and other HPV16 related types.

INTRODUCTION: In 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9-13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV. METHODS: Women aged 18-22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019-January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV. RESULTS: A total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load. CONCLUSIONS: Over one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI 60-71%) for UTD, 33% (95% CI 18-46%) for 2 doses-not UTD, and 40% (95% CI 27-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI 64-79%) for UTD, 39% (95% CI 10-58%) for 2 doses-not UTD, and 48% (95% CI 25-63%) for 1 dose. VE was higher for vaccination at age <20 than {greater than or equal to}20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(†) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(§) In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation(¶) for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine,(†) and the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for their use in persons aged ≥16 years and ≥18 years, respectively.(§) In May 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; ACIP recommends that all persons aged ≥12 years receive a COVID-19 vaccine. Both Pfizer-BioNTech and Moderna vaccines are mRNA vaccines encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines were authorized and recommended as a 2-dose schedule, with second doses administered 21 days (Pfizer-BioNTech) or 28 days (Moderna) after the first dose. After reports of myocarditis and pericarditis in mRNA vaccine recipients,(¶) which predominantly occurred in young males after the second dose, an ACIP meeting was rapidly convened to review reported cases of myocarditis and pericarditis and discuss the benefits and risks of mRNA COVID-19 vaccination in the United States. Myocarditis is an inflammation of the heart muscle; if it is accompanied by pericarditis, an inflammation of the thin tissue surrounding the heart (the pericardium), it is referred to as myopericarditis. Hereafter, myocarditis is used to refer to myocarditis, pericarditis, or myopericarditis. On June 23, 2021, after reviewing available evidence including that for risks of myocarditis, ACIP determined that the benefits of using mRNA COVID-19 vaccines under the FDA's EUA clearly outweigh the risks in all populations, including adolescents and young adults. The EUA has been modified to include information on myocarditis after receipt of mRNA COVID-19 vaccines. The EUA fact sheets should be provided before vaccination; in addition, CDC has developed patient and provider education materials about the possibility of myocarditis and symptoms of concern, to ensure prompt recognition and management of myocarditis.

BACKGROUND: Apparent associations between HPV prevalence and age observed in cross-sectional studies could be misleading if cohort effects influence HPV detection. METHODS: Using data from 2003-2016 National Health and Nutrition Examination Surveys (NHANES), we evaluated overall and 10-year birth cohort-specific cervicovaginal HPV prevalence estimates (any, high-risk [HR], and non-HR) by 3-year age group among 27-59 year-old females born in 1950-1979. Average percent changes (APC) in HPV prevalence by 3-year age were calculated using prevalence ratios from log-binomial models. RESULTS: Overall, prevalence of any HPV declined from 49.9% in 27-29 year-olds to 33.8% in 57-59 year-olds [APC: -2.82% per 3-year age group, 95% confidence interval (CI): -4.02%, -1.60%] as did prevalence of HR-HPV [APC: -6.19% (95% CI: -8.09%, -4.26%)] and non-HR-HPV [APC: -2.00% (95% CI: -3.48%, -0.51%)]. By birth cohort, declines by age group were seen in prevalences of any HPV, HR-HPV, and non-HR-HPV for those born in the 1950s and 1970s and in any HPV and HR-HPV for those born in the 1960s (APC range: -14.08% - 0.06%). CONCLUSIONS: Declines in HPV prevalence with age in these cross-sectional surveys cannot be explained by birth cohort differences alone, as associations were observed across all birth cohorts. These findings are consistent with biological and behavioral explanations.

BACKGROUND: Patterns of human papillomavirus (HPV) prevalence by age differ by sex. To further the descriptive epidemiology of genital HPV, we analyzed prevalence by age for non-vaccine-(non-4vHPV)-type and vaccine-(4vHPV)-type HPV by sex using 2013-2016 National Health and Nutrition Examination Survey data, the first 4 years of national data from both sexes. METHODS: Penile and cervicovaginal swabs were self-collected from 15-59-year-olds and tested for 37 HPV types. 4vHPV-type (6/11/16/18) and non-4vHPV-type (any of 33 other types) prevalences were estimated by 3-year age group and participant characteristics. Average percent changes (APC) in prevalence were estimated using segmented log-binomial regression. RESULTS: Among females, a positive relationship between non-4vHPV-type prevalence and age was seen from 15-17 to 21-23 years (APC: 56.5), followed by a negative relationship through 30-32 years (APC: -13.2); thereafter, prevalence was not related to age. 4vHPV-type prevalence was positively related to age through 24-26 years (APC: 56.9), then negatively related through 57-59 years (APC: -6.0). Among males, non-4vHPV-type prevalence had a positive relationship with age through 21-23 years (APC: 102.4) with a smaller positive relationship through 57-59 years (APC: 1.4). For both sexes, modeled joinpoints for 4vHPV-type prevalence occurred at older ages compared to joinpoints for non-4vHPV-type prevalence. CONCLUSIONS: Sex differences in age-specific non-vaccine-type HPV prevalence may reflect natural history and sexual behavior. Differences in vaccine-type and non-vaccine-type modeling results suggest vaccine impact as joinpoints occur in mid-late-20s for vaccine-type HPV but early-20s for non-vaccine-types. These data can assist in refining HPV vaccination models and inform HPV vaccination practices and policy.

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, Inc; Philadelphia, Pennsylvania) in persons aged ≥16 years (1); on December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the vaccine in the same age group (2). As of May 12, 2021, approximately 141.6 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥16 years.* On May 10, 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years (1). On May 12, 2021, ACIP issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(§) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥12 years under an EUA is interim and will be updated as additional information becomes available.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged <50 years, as well as the availability of alternative COVID-19 vaccines, is required to guide vaccine decision-making and ensure early recognition and clinical management of TTS.

OBJECTIVE: The aim of the study was to describe trends in human papillomavirus (HPV) testing preceding diagnosis of cervical precancer during a time of changing screening recommendations. MATERIALS AND METHODS: We conducted a cross-sectional analysis of data from active, population-based, laboratory surveillance among 1.5 million residents of 5 areas in the United States. We included women aged 21-39 years diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ (collectively, CIN2+) during 2008-2016, who had a cytology and/or HPV test before diagnosis (n = 16,359). RESULTS: The proportion of women with an HPV test preceding CIN2+ increased from 42.9% in 2008 to 73.3% in 2016 (p < .01); testing increased in all age groups (21-24 y: 35.3% to 47.6%, 25-29 y: 40.9% to 64.1%, 30-39 y: 51.7% to 85.9%, all p < .01). The HPV testing varied by cytology result and was highest among women with atypical squamous cells of unknown significance (n = 4,310/4,629, 93.1%), negative for intraepithelial lesion or malignancy (n = 446/517, 86.3%), and atypical glandular cells (n = 145/257, 56.4%). By 2016, at least half of all cases in every surveillance area had an HPV test before diagnosis. CONCLUSIONS: During 2008-2016, the proportion of women with an HPV test preceding CIN2+ increased significantly for all age groups, cytology results, and surveillance areas. By 2016, most (85.9%) women aged 30-39 years had an HPV test, consistent with recommendations. Increasing utilization of HPV tests, which have demonstrated improved sensitivity for detecting cervical disease, may in part explain increasing rates of cervical precancer among women 30 years and older.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (1). Although most infections resolve without clinical sequalae, persistent HPV infection can cause cervical, other anogenital, and oropharyngeal cancers and anogenital warts. HPV vaccination has been recommended in the United States at age 11-12 years since 2006 for females and since 2011 for males. Catch-up vaccination is recommended through age 26 years.* A quadrivalent vaccine (4vHPV) targeting types 6, 11, 16, and 18 was mainly used until 2015, when a 9-valent vaccine (9vHPV), targeting the same four types as 4vHPV and five additional types (31, 33, 45, 52, and 58), was introduced; 9vHPV has been the only vaccine available in the United States since the end of 2016 (2). HPV vaccination coverage has increased but remains lower than that of other vaccinations recommended for adolescents (3). A decrease in prevalence of 4vHPV types detected in cervicovaginal swabs among young females from the prevaccine era (2003-2006) to 2007-2010 in the National Health and Nutrition Examination Survey (NHANES) was an early indicator of vaccine impact (2) and was also observed in later periods (4,5). NHANES data from 2017-2018 were included in this analysis to update HPV prevalence estimates among females aged 14-34 years. From the prevaccine era to 2015-2018, significant decreases in 4vHPV-type prevalence occurred among females aged 14-19 years (88%) and 20-24 years (81%). In sexually experienced females, 4vHPV-type prevalence decreased in those who reported receiving ≥1 HPV vaccine dose (97% among those aged 14-19 years, 86% among those aged 20-24 years) and in those who reported no vaccination (87% among those aged 14-19 years, 65% among those aged 20-24 years). Significant declines among unvaccinated females suggest herd effects. These data show increasing impact of HPV vaccination in the United States. HPV vaccination is a critical prevention tool against HPV infection, anogenital warts, and HPV-attributable precancers and cancers. HPV vaccination is highly effective and is recommended routinely at age 11-12 years and through 26 years for persons not already vaccinated.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc, a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey). The Janssen COVID-19 vaccine is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector vaccine, encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19 (1). Vaccination with the Janssen COVID-19 vaccine consists of a single dose (5 × 1010 virus particles per 0.5-mL dose) administered intramuscularly. On February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Janssen COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. This vaccine is the third COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendations (EtR) framework,† following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.§ The ACIP recommendation for the use of the Janssen COVID-19 vaccine under an EUA is interim and will be updated as additional information becomes available.

BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States (US) were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the US for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by gender and age group. Primary estimates are represented by medians and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1=66.6, Q3=68.7) million prevalent and 26.2 (Q1=24.0, Q3=28.7) million incident STIs in the US. Chlamydia, trichomoniasis, genital herpes, and HPV comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15-24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the US is high. Almost half of incident STIs occurred in persons aged 15-24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

INTRODUCTION: Human papillomavirus (HPV) can cause anogenital warts and several types of cancer, including cervical cancers and precancers. We estimated the prevalence, incidence, and number of persons with prevalent and incident HPV infections in the United States in 2018. METHODS: Prevalence and incidence were estimated for infections with any HPV (any of 37 types detected using Linear Array) and disease-associated HPV, two types that cause anogenital warts plus 14 types detected by tests used for cervical cancer screening (HPV 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the 2013-2016 National Health and Nutrition Examination Survey to estimate prevalence among 15-59-year-olds, overall and by sex. Incidences in 2018 were estimated per 10,000 persons using an individual-based transmission-dynamic type-specific model calibrated to US data. We estimated number of infected persons by applying prevalences and incidences to 2018 US population estimates. RESULTS: Prevalence of infection with any HPV was 40.0% overall, 41.8% in males and 38.4% in females; prevalence of infection with disease-associated HPV was 24.2% in males and 19.9% in females. An estimated 23.4 and 19.2 million males and females had a disease-associated HPV type infection in 2018. Incidences of any and disease-associated HPV infection were 1222 and 672 per 10,000 persons; incidence of disease-associated HPV infection was 708 per 10,000 males and 636 per 10,000 females. An estimated 6.9 and 6.1 million males and females had an incident infection with a disease-associated HPV type in 2018. CONCLUSIONS: We document a high HPV burden of infection in the United States in 2018, with 42 million persons infected with disease-associated HPV and 13 million persons acquiring a new infection. While most infections clear, some disease-associated HPV type infections progress to disease. The HPV burden highlights the need for continued monitoring of HPV-associated cancers, cervical cancer screening, and HPV vaccination to track and prevent disease.

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million-12.0 million), results in 601,000 ED visits (95% CrI 364,000-866,000), 118,000 hospitalizations (95% CrI 86,800-150,000), and 6,630 deaths (95% CrI 4,520-8,870) and incurring US $3.33 billion (95% CrI 1.37 billion-8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.

On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts), a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). This vaccine is the second COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). Vaccination with the Moderna COVID-19 vaccine consists of 2 doses (100 μg, 0.5 mL each) administered intramuscularly, 1 month (4 weeks) apart. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Moderna COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,(†) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.(§) Use of all COVID-19 vaccines authorized under an EUA, including the Moderna COVID-19 vaccine, should be implemented in conjunction with ACIP's interim recommendations for allocating initial supplies of COVID-19 vaccines (3). The ACIP recommendation for the use of the Moderna COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 doses (30 μg, 0.3 mL each) administered intramuscularly, 3 weeks apart. On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,(†) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(§) The recommendation for the Pfizer-BioNTech COVID-19 vaccine should be implemented in conjunction with ACIP's interim recommendation for allocating initial supplies of COVID-19 vaccines (2). The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

INTRODUCTION: This analysis evaluates trends in cervical lesions with human papillomavirus 16/18 detected by area-based measures of race, ethnicity, and poverty during 2008-2015. METHODS: Trends in the proportion of lesions with human papillomavirus 16/18 detected among residents of New Haven County, Connecticut were examined by area-based measures of race, ethnicity, and poverty. Area-based measures are aggregate descriptors of census tract characteristics useful for measuring differences in health outcomes in the context of where people live. Multivariable logistic regression modeling was conducted, adjusted for individual-level race, ethnicity, and insurance status to assess the independent effects of area-based measures. Data were analyzed in 2018-2019. RESULTS: Among women aged 21-24 years and 25-29 years, significant declines in the proportion of lesions with human papillomavirus 16/18 were observed. Among women aged 21-24 years, declines began earlier and were greater in magnitude in areas of lower poverty (OR=0.55, 95% CI=0.36, 0.85 for 2010-2012 vs 2008-2009 and OR=0.30, 95% CI=0.18, 0.51 for 2013-2015 vs 2008-2009) compared with higher poverty (OR=1.66, 95% CI=0.86, 3.21 and OR=0.48, 95% CI=0.19, 1.20). Similar patterns were observed for women aged 25-29 years, and for area-based measures of race and ethnicity. CONCLUSIONS: Differences were observed in declines in the proportion of human papillomavirus 16/18 lesions by area-based measures since the introduction of human papillomavirus vaccines, with greater and earlier declines in areas with fewer residents living in poverty and racial minorities. Ongoing human papillomavirus vaccine impact monitoring is necessary to track differences by sociodemographic characteristics.

Before 2016, human papillomavirus (HPV) vaccination was recommended in a three-dose schedule; however, many vaccine-eligible U.S. females received <3 doses, providing an opportunity to evaluate real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia grades 2-3 and adenocarcinoma in situ (CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT), 2008-2014. Archived tissue from CIN2+ lesions was tested for 37 HPV types. Women were classified by number of doses received >/=24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1-adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with all other CIN2+ (controls). Among 3,300 women with CIN2+, typing results, and vaccine history available, 1,561 (47%) were HPV-16/18 positive, 136 received (4%) 1 dose, 108 (3%) 2 doses, and 325 (10%) 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval: 0.37, 0.76; VE=47%), 0.45 (95% confidence interval: 0.30, 0.69; VE=55%), and 0.26 (95% confidence interval 0.20, 0.35; VE=74%). We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.

We evaluated racial/ethnic differences in prevalence of oncogenic HPV types targeted by the quadrivalent HPV vaccine (16/18) and nonavalent HPV vaccine (31/33/45/52/58) in women diagnosed with CIN2/3/AIS after quadrivalent HPV vaccine introduction (2008-2015). Typing data from 1810 cervical tissue specimen from HPV-IMPACT (Alameda County, California, US), a population-based CIN2/3/AIS surveillance effort, were analyzed. Using log-binomial regression, we calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) comparing type prevalence by race/ethnicity, adjusted for health insurance, age, CIN2/3/AIS grade, and time period, overall and in the "early vaccine era" (2008-2011) and "later vaccine era" (2012-2015). Overall, oncogenic HPV16/18 prevalence was significantly lower among black (43%) and Hispanic (43%) women compared with white (52%) women (aPR (95% CI): 0.80 (0.70, 0.93) and 0.80 (0.70, 0.91), respectively). In 2008-2011, proportion of HPV16/18 detected was significantly lower in black (47%), Hispanic (46%), and Asian (42%) women compared to white (58%) women (aPR (95% CI): 0.80 (0.67, 0.96), 0.75 (0.63, 0.90), and 0.73 (0.58, 0.90), respectively). There were no significant differences in 2012-2015. Between the two eras, HPV16/18 prevalence declined in white (-11%), black (-9%), and Hispanic (-6%) women, and increased in Asian women (12%). Decreasing HPV 16/18 prevalence in CIN2/3/AIS lesions in white, black, and Hispanic women may suggest benefit from quadrivalent vaccination. In our unadjusted analysis of HPV31/33/45/52/58, prevalence did not differ significantly by race/ethnicity, but was significantly higher among Hispanic women (32%) compared to white women (27%) after adjustment (aPR (95%CI): 1.22 (1.02, 1.47). Prevalence was also non-significantly higher among black (32%) and Asian (33%) women. This analysis suggests that the nonavalent vaccine's potential for impact against cervical precancers will not be lower in women of color compared to white women. These data underscore the importance of equitable vaccination in facilitating continued declines of vaccine-preventable HPV types among all women.

PURPOSE: To monitor human papillomavirus (HPV) vaccine impact in the U.S., we evaluated quadrivalent vaccine (4vHPV)-type prevalence among females aged 14-34 years in the prevaccine (2003-2006) and vaccine (2013-2016) eras overall and by race/ethnicity in the National Health and Nutrition Examination Survey. METHODS: We analyzed HPV DNA prevalence in self-collected cervicovaginal specimens, demographic characteristics, sexual behavior, and self-reported/parent-reported vaccination status. We compared prevaccine to vaccine era 4vHPV-type prevalence, using unadjusted and adjusted prevalence ratios (PR and aPR) and 95% confidence intervals (CIs). PRs were calculated by race/ethnicity (non-Hispanic white [NHW], non-Hispanic black [NHB], and Mexican American [MA]). Overall aPRs were adjusted for race/ethnicity, lifetime sex partners, and poverty. RESULTS: Overall, 4,674 females had HPV typing results; 3,915 reported NHW, NHB, or MA race/ethnicity. Vaccination coverage of >/=1 dose was 53.9% among 14- to 19-year-olds (NHW 52.6%, NHB 58.1%, and MA 59.5%) and 51.5% among 20- to 24-year-olds (NHW 58.8%, NHB 45.0%, MA 33.8%). Among 14- to 19-year-olds, 4vHPV-type prevalence decreased overall (11.5% to 1.8%; aPR = .14 [CI: .08-.24]) and in NHW (PR = .14 [CI: .06-.29]), NHB (PR = .26 [CI: .12-.54]), and MA (PR = .13 [CI: .03-.53]). In 20- to 24-year-olds, 4vHPV-type prevalence decreased overall (18.5% to 5.3%; aPR = .29 [CI: .15-.56]) and in NHW (PR = .27 [CI: .11-.67]) and NHB (PR = .38 [CI: .18-.80]). No significant declines were observed in older age groups. CONCLUSIONS: Within 10 years of vaccine introduction, 4vHPV-type prevalence declined 86% among 14- to 19-year-olds, with declines observed in NHW, NHB, and MA females, and 71% among 20- to 24-year-olds, with declines in NHW and NHB females. These extraordinary declines should lead to substantial reductions in HPV-associated cancers.