HPV type-specific trends in cervical precancers in the United States, 2008 to 2016.

Declines in cervical intraepithelial neoplasia grades 2 to 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 to 39 years, 2008 to 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 nonvaccine 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 nonvaccine vs vaccine HR-HPV types. No significant declining trends were observed in older age groups. In 2015-2016 compared with 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.

Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. METHODS: We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture. RESULTS: We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4-44.3%) and 33.6% (IQR 22.9-43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions. CONCLUSION: These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.

Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018.

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.

Prevalence of Human Papillomavirus Among Women Older than Recommended Age for Vaccination by Birth Cohort, United States 2003‒2016.

BACKGROUND: Apparent associations between human papillomavirus (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, 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 to 59-year-old women born in 1950-1979. Average percent changes (APC) in HPV prevalence by 3-year age were calculated. 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% to -1.60%) as did prevalence of HR-HPV (APC, -6.19%; 95% CI, -8.09% to -4.26%) and non-HR-HPV (APC, -2.00%; 95% CI, -3.48% to -.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% to 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.

Effectiveness of Human Papillomavirus (HPV) Vaccination Against Penile HPV Infection in Men Who Have Sex With Men and Transgender Women.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended since 2011 for boys aged 11-12 years, with catch-up vaccination recommended through age 26 years for previously unvaccinated men who have sex with men (MSM). METHODS: During 2016-2018, a cross-sectional study enrolled MSM and transgender women aged 18-26 years in Seattle, Washington. Participants submitted self-collected penile swab specimens for HPV genotyping. HPV vaccination history was self-reported. We compared HPV prevalence among vaccinated participants with that in participants with no or unknown vaccination history, using log-binomial regression to estimate adjusted prevalence ratios and confidence intervals. RESULTS: Among 687 participants, 348 (50.7%) self-reported ever receiving ≥1 HPV vaccine dose; the median age at first HPV vaccination was 21 years, and the median age at first sex, 17 years. Overall, the prevalence of penile quadrivalent HPV vaccine (4vHPV)-type HPV was similar in vaccinated participants (12.1%) and participants with no or unknown vaccination (15.6%) (adjusted prevalence ratio, 0.69 [95% confidence interval, .47-1.01]). However, the prevalence was significantly lower in participants vaccinated at age ≤18 years than in those with no of unknown vaccination (0.15 [.04-.62]), corresponding to a vaccine effectiveness of 85% against 4vHPV-type HPV. CONCLUSIONS: Results suggest that HPV vaccination is effective in preventing penile HPV infections in young MSM when administered at age ≤18 years.

HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring.

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.

Changes in Cervical Cytology Results and Human Papillomavirus Types Among Persons Screened for Cervical Cancer, 2007 and 2015-2017.

OBJECTIVES: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007. MATERIALS AND METHODS: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017. RESULTS: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups. CONCLUSIONS: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.

Prevalence of human papillomavirus genotypes in high-grade cervical precancer and invasive cervical cancer from cancer registries before and after vaccine introduction in the United States.

BACKGROUND: US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability. METHODS: Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type-specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors. RESULTS: A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers. CONCLUSIONS: The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

Genital Human Papillomavirus Prevalence Over the Lifespan Among Females and Males in a National Cross-Sectional Survey, United States, 2013-2016.

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 nonvaccine (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- to 59-year-olds and tested for 37 HPV types. The 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 (APCs) 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. The 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 with 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 nonvaccine types. These data can assist in refining HPV vaccination models and inform HPV vaccination practices and policy.

Sexual Positioning Practices and Anal Human Papillomavirus Infection Among Young Men Who Have Sex with Men and Transgender Women-Chicago, Illinois, 2016-2018.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States; men who have sex with men (MSM) have higher prevalence of infection and related disease compared with other men. We assessed whether differences in HPV acquisition exist among MSM according to their sexual positioning practices, as well as self-reported receipt of HPV vaccination. METHODS: We enrolled young MSM and transgender women aged 18 to 26 years in Chicago, IL (N = 666). Participants self-reported their history of HPV vaccination and submitted self-collected anal swab specimens for type-specific HPV detection using an L1-consensus PCR assay. Multivariable logistic regression analyses were used to assess relationships between sexual positioning practices and detection of any HPV or quadrivalent HPV vaccine (4vHPV) types by vaccination status, defined as self-reported receipt of ≥1 HPV vaccine dose versus none. RESULTS: Among 666 participants, 400 (60.1%) had any anal HPV, and 146 (21.9%) had a 4vHPV type. Among vaccinated participants, 18, 36, and 177 reported exclusively insertive, exclusively receptive, or both sexual positioning practices, respectively. Compared with participants reporting exclusively insertive anal sex, odds of any HPV were significantly higher among participants engaging exclusively in receptive anal sex (adjusted odds ratio [aOR], 5.90; 95% confidence interval [CI], 2.52-13.78), as well as those engaging in both (aOR, 3.32; 95% CI, 1.71-6.44). Vaccinated participants, compared with unvaccinated participants, had lower odds of 4vHPV-type HPV regardless of sexual positioning practices (aOR, 0.56; 95% CI, 0.34-0.92). CONCLUSIONS: Adult men and transgender women who practice anal receptive sex have high prevalence of infection with any HPV. Routine vaccination of all adolescents is expected to reduce HPV-related disease incidence among adult MSM and transgender women as vaccinated cohorts age.

Estimated Prevalence and Incidence of Disease-Associated Human Papillomavirus Types Among 15- to 59-Year-Olds in the United States.

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, 2 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- to 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 men, and 38.4% in women; prevalence of infection with disease-associated HPV was 24.2% in men and 19.9% in women. An estimated 23.4 and 19.2 million men and women 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 men and 636 per 10,000 women. An estimated 6.9 and 6.1 million men and women 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. Although 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.

Declines in Prevalence of Human Papillomavirus Vaccine-Type Infection Among Females after Introduction of Vaccine - United States, 2003-2018.

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.

Human Papillomavirus Vaccine Effectiveness Against HPV Infection: Evaluation of One, Two, and Three Doses.

BACKGROUND: Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses. METHODS: We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses. RESULTS: Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12). CONCLUSIONS: Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses.

Vaccine Effectiveness Against Prevalent Anal and Oral Human Papillomavirus Infection Among Men Who Have Sex With Men-United States, 2016-2018.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended for young adult men who have sex with men (MSM) since 2011. METHODS: The Vaccine Impact in Men study surveyed MSM and transgender women aged 18-26 years in 3 US cities during 2016-2018. Self-collected anal swab and oral rinse specimens were assessed for 37 types of HPV. We compared HPV prevalence among vaccinated and unvaccinated participants and determined adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). RESULTS: Among 1767 participants, 704 (39.8%) self-reported receiving HPV vaccine. Median age at vaccination (18.7 years) was older than age at first sex (15.7 years). Quadrivalent vaccine-type HPV was detected in anal or oral specimens from 475 (26.9%) participants. Vaccine-type HPV prevalence was lower among vaccinated (22.9%) compared with unvaccinated (31.6%) participants; aPR for those who initiated vaccination at age ≤18 years was 0.41 (CI, 0.24-0.57) and at age >18 years was 0.82 (CI, 0.67-0.98). Vaccine effectiveness of at least 1 HPV vaccine dose at age ≤18 years or >18 years was 59% and 18%, respectively. CONCLUSIONS: Findings suggest real-world effectiveness of HPV vaccination among young adult MSM. This effect was stronger with younger age at vaccination.

Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women - United States, 2008 and 2016.

Human papillomavirus (HPV) causes approximately 30,000 cancers in the United States annually (1). HPV vaccination was introduced in 2006 to prevent HPV-associated cancers and diseases (1). Cervical cancer is the most common HPV-associated cancer in women (1). Whereas HPV-associated cancers typically take decades to develop, screen-detected high-grade cervical lesions (cervical intraepithelial neoplasia grades 2 [CIN2], 3 [CIN3], and adenocarcinoma in situ, collectively CIN2+) develop within a few years after infection and have been used to monitor HPV vaccine impact (1-3). CDC analyzed data from the Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT), a population-based CIN2+ surveillance system, to describe rates of CIN2+ among women aged ≥18 years during 2008-2016. Age-specific rates were applied to U.S. population data to estimate the total number of CIN2+ cases diagnosed in the United States in 2008* and in 2016. From 2008 to 2016, the rate of CIN2+ per 100,000 women declined significantly in women aged 18-19 years and 20-24 years and increased significantly in women aged 40-64 years. In the United States in 2008, an estimated 216,000 (95% confidence interval [CI] = 194,000-241,000) CIN2+ cases were diagnosed, 55% of which were in women aged 18-29 years; in 2016, an estimated 196,000 (95% CI = 176,000-221,000) CIN2+ cases were diagnosed, 36% of which were in women aged 18-29 years. During 2008 and 2016, an estimated 76% of CIN2+ cases were attributable to HPV types targeted by the vaccine currently used in the United States. These estimates of CIN2+ cases likely reflect changes in CIN2+ detection resulting from updated cervical cancer screening and management recommendations, as well as primary prevention through HPV vaccination. Increasing coverage of HPV vaccination in females at the routine age of 11 or 12 years and catch-up vaccination through age 26 years will contribute to further reduction in cervical precancers.

Label-Free and Continuous-Flow Ferrohydrodynamic Separation of HeLa Cells and Blood Cells in Biocompatible Ferrofluids.

In this study, a label-free, low-cost, and fast ferrohydrodynamic cell separation scheme is demonstrated using HeLa cells (an epithelial cell line) and red blood cells. The separation is based on cell size difference, and conducted in a custom-made biocompatible ferrofluid that retains the viability of cells during and after the assay for downstream analysis. The scheme offers moderate-throughput (≈106 cells h-1 for a single channel device) and extremely high recovery rate (>99%) without the use of any label. It is envisioned that this separation scheme will have clinical applications in settings where rapid cell enrichment and removal of contaminating blood will improve efficiency of screening and diagnosis such as cervical cancer screening based on mixed populations in exfoliated samples.

High impact of quadrivalent human papillomavirus vaccine across racial/ethnic groups: National Health and Nutrition Examination Survey, 2003-2006 and 2015-2018.

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.

Human papillomavirus negative high grade cervical lesions and cancers: Suggested guidance for HPV testing quality assurance.

BACKGROUND: Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL). METHODS: There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process. RESULT: Standard PCR testing detected HPV in 55.2 % (64/116) of initially "HPV-negative" samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented. CONCLUSION: Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of "HPV negative" HSIL+ samples.