Estimates of Incidence and Predictors of Fatiguing Illness after SARS-CoV-2 Infection.

This study aimed to estimate the incidence rates of post-COVID-19 fatigue and chronic fatigue and to quantify the additional incident fatigue caused by COVID-19. We analyzed electronic health records data of 4,589 patients with confirmed COVID-19 during February 2020-February 2021 who were followed for a median of 11.4 (interquartile range 7.8-15.5) months and compared them to data from 9,022 propensity score-matched non-COVID-19 controls. Among COVID-19 patients (15% hospitalized for acute COVID-19), the incidence rate of fatigue was 10.2/100 person-years and the rate of chronic fatigue was 1.8/100 person-years. Compared with non-COVID-19 controls, the hazard ratios were 1.68 (95% CI 1.48-1.92) for fatigue and 4.32 (95% CI 2.90-6.43) for chronic fatigue. The observed association between COVID-19 and the significant increase in the incidence of fatigue and chronic fatigue reinforces the need for public health actions to prevent SARS-CoV-2 infections.

Determinants of Type-Specific Human Papillomavirus Concordance Across Anatomic Sites in Young Men Who Have Sex With Men and Transgender Women, 3 U.S. Cities, 2016-2018.

BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

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.

Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study.

Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first-void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first-void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type-specific antibody responses to the 9vHPV types were analyzed in 174 first-void urine and 172 serum samples using a virus-like particle-based IgG multiplex enzyme-linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%-100% of first-void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%-100% of first-void urine and 98%-100% of serum samples had HPV-specific antibody concentrations. Results show significant Spearman rank correlations between type-specific HPV-antibody concentrations for paired first-void urine and serum at all time points. This study confirms the potential feasibility of utilizing first-void urine as a noninvasive immunological sample within HPV vaccine trials.

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.

Physiological assessment of orthostatic intolerance in chronic fatigue syndrome.

BACKGROUND: Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia. OBJECTIVE: Evaluate the physiologic response of patients with ME/CFS to a standardized OC. DESIGN: Respiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of  ≥ 20 breaths per minute-either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2. PATIENTS: 63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29). MEASURES: Supine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension. RESULTS: The majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia. CONCLUSIONS: The 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.

Sensitivity of Self-Reported Human Papillomavirus Vaccination History Among 18- to 26-Year-Old Men Who Have Sex With Men: Seattle, WA, 2016 to 2018.

BACKGROUND: We assessed the sensitivity of self-reported human papillomavirus (HPV) vaccination among young adult men who have sex with men (MSM) with documented HPV vaccination. METHODS: During 2016-2018, MSM and transgender women aged 18 to 26 years were enrolled in Seattle, WA. A history of HPV vaccination was assessed via self-administered survey, clinic electronic medical records, and the Washington State Immunization Information System. We assessed self-report sensitivity among participants with documented prior HPV vaccination (≥1 dose) in either the electronic medical record or the Washington State Immunization Information System, and used logistic regression to compare sensitivity by age, number of doses, and time since first dose. RESULTS: Of 292 participants with ≥1 documented HPV vaccine dose, 243 self-reported ≥1 dose (sensitivity, 83.2%; 95% confidence interval [CI], 78.4%-87.3%). Compared with participants whose first dose was <1 year ago, the likelihood of self-report was lower among those with ≥3 years since first dose (adjusted odds ratio [aOR], 0.2; 95% CI, 0.1-0.5). Furthermore, compared with participants with only 1 documented HPV vaccine dose, the likelihood of self-reporting ≥1 dose was higher among those with 2 (aOR, 2.4; 95% CI, 1.0-5.5) or ≥3 doses (aOR, 6.2; 95% CI, 2.7-14.4). Among 115 participants with ≥3 documented doses, sensitivity for recalling ≥3 doses was 69.6% (95% CI, 60.3%-77.8%). CONCLUSIONS: Most young adult MSM with a documented history of HPV vaccination self-reported prior HPV vaccination. Although recall was highest in those with ≥3 doses, 30% of this fully vaccinated subgroup did not correctly recall the number of doses received, highlighting limitations of self-reporting. Furthermore, results indicating reduced recall with ≥3 years since first dose suggest that sensitivity of self-report among young adult MSM may decline over time as adolescent vaccination coverage increases.

Risk-Based Cervical Consensus Guidelines: Methods to Determine Management if Less Than 5 Years of Data Are Available.

OBJECTIVES: In the 2019 ASCCP Risk-Based Management Consensus Guidelines, clinical management decisions are based on immediate and 5-year cervical intraepithelial neoplasia (CIN) 3+ risk estimates. However, data for technologies other than human papillomavirus testing and cytology may be limited to clinical trials and observational studies of shorter duration than 5 years. To enable decisions about 1- or 3-year intervals, 3-year CIN 3+ risk equivalents to 5-year CIN 3+ risk thresholds were generated. MATERIALS AND METHODS: We examined screening test result scenarios around the 5-year risk thresholds of 0.15% and 0.55% and calculated the average percent increase in CIN 3+ risk from 3 to 5 years. Using this average increase, we obtained estimates of corresponding risk thresholds at 3 years. We then validated whether use of the 3-year risk threshold would have resulted in equivalent management per the 2019 recommendations. RESULTS: Around the 5-year CIN 3+ risk threshold of 0.55%, the average increase in risk from 3 to 5 years was 0.16%. Therefore, the equivalent threshold for 3-year risk was estimated as 0.39%. We found no difference in recommendations to return in 1 or 3 years using the 3-year or 5-year risk thresholds in 66 of the 67 scenarios (98.5%) in follow-up in 2019 guidelines. CONCLUSIONS: In this methodological addendum, the Enduring Guidelines Committee adopted the use of the 0.39% 3-year CIN 3+ risk threshold as equivalent of the 0.55% 5-year CIN 3+ risk threshold for technologies with fewer than 5 years of follow-up data. This allows evidence-based guidance for surveillance intervals of 1 or 3 years for new technologies with limited longitudinal data.

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.

Significant Declines in Juvenile-onset Recurrent Respiratory Papillomatosis Following Human Papillomavirus (HPV) Vaccine Introduction in the United States.

BACKGROUND: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare and serious disease caused by human papillomavirus (HPV) presumably acquired during vaginal delivery. HPV vaccination of females through age 26 years, recommended in the United States since 2006, can prevent HPV transmission. We assessed trends in JORRP cases before and after HPV vaccine introduction in the United States. METHODS: Case-patients were identified from 26 pediatric otolaryngology centers in 23 U.S. states. Demographics and clinical history were abstracted from medical records. Case-patients were grouped by year of birth, and birth-cohort incidences were calculated using number of births from either national or state-level natality data from the 23 states. We calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) in 2-year intervals. RESULTS: We identified 576 U.S. JORRP case-patients born in 2004-2013. Median age at diagnosis was 3.4 years (interquartile range: 1.9, 5.5). Number of identified JORRP case-patients declined from a baseline of 165 born in 2004-2005 to 36 born in 2012-2013. Incidence of JORRP per 100 000 births using national data declined from 2.0 cases in 2004-2005 to 0.5 cases in 2012-2013 (IRR = 0.2, 95% CI = .1-.4); incidence using state-level data declined from 2.9 cases in 2004-2005 to 0.7 cases in 2012-2013 (IRR = 0.2, 95% CI = .1-.4). CONCLUSIONS: Over a decade, numbers of JORRP case-patients and incidences declined significantly. Incidences calculated using national denominator data are likely underestimates; those calculated using state-level denominator data could be overestimates. These declines are most likely due to HPV vaccination. Increasing vaccination uptake could lead to elimination of this HPV-related disease.

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.

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.