Sean Schafer

Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States – 2008–2012☆

BACKGROUND Prevention of pre-invasive cervical lesions is an important benefit of HPV vaccines, but demonstrating impact on these lesions is impeded by changes in cervical cancer screening. Monitoring vaccine-types associated with lesions can help distinguish vaccine impact from screening effects. We examined trends in prevalence of HPV 16/18 types detected in cervical intraepithelial neoplasia 2, 3, and adenocarcinoma in situ (CIN2+) among women diagnosed with CIN2+ from 2008 to 2012 by vaccination status. We estimated vaccine effectiveness against HPV 16/18-attributable CIN2+ among women who received ≥1 dose by increasing time intervals between date of first vaccination and the screening test that led to detection of CIN2+ lesion. METHODS Data are from a population-based sentinel surveillance system to monitor HPV vaccine impact on type-specific CIN2+ among adult female residents of five catchment areas in California, Connecticut, New York, Oregon, and Tennessee. Vaccination and cervical cancer screening information was retrieved. Archived diagnostic specimens were obtained from reporting laboratories for HPV DNA typing. RESULTS From 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly decreased from 53.6% to 28.4% among women who received at least one dose (Ptrend<.001) but not among unvaccinated women (57.1% vs 52.5%; Ptrend=.08) or women with unknown vaccination status (55.0% vs 50.5%; Ptrend=.71). Estimated vaccine effectiveness for prevention of HPV 16/18-attributable CIN2+ was 21% (95% CI: 1-37), 49% (95% CI: 28-64), and 72% (95% CI: 45-86) in women who initiated vaccination 25-36 months, 37-48 months, and >48 months prior to the screening test that led to CIN2+ diagnosis. CONCLUSIONS Population-based data from the United States indicate significant reductions in CIN2+ lesions attributable to types targeted by the vaccines and increasing HPV vaccine effectiveness with increasing interval between first vaccination and earliest detection of cervical disease.

Population-based Incidence of Pulmonary Nontuberculous Mycobacterial Disease in Oregon 2007 to 2012

RATIONALE Pulmonary nontuberculous mycobacteria (NTM) disease is a chronic, nonreportable illness, making it difficult to monitor. Although recent studies suggest an increasing prevalence of NTM disease in the United States, the incidence and temporal trends are unknown. OBJECTIVES To describe incident cases and calculate the incidence and temporal trends of pulmonary NTM disease in Oregon. METHODS We contacted all laboratories performing mycobacterial cultures on Oregon residents and collected demographic and specimen information for patients with NTM isolated during 2007 to 2012. We defined a case of pulmonary NTM disease using the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. We used similar state-wide mycobacterial laboratory data from 2005 to 2006 to exclude prevalent cases from our calculations. We calculated annual pulmonary NTM disease incidence within Oregon during 2007 to 2012, described cases demographically and microbiologically, and evaluated incidence trends over time using a Poisson model. MEASUREMENTS AND MAIN RESULTS We identified 1,146 incident pulmonary NTM cases in Oregon residents from 2007 to 2012. The median age was 69 years (range, 0.9-97 yr). Cases were more likely female (56%), but among patients less than 60 years old, disease was more common in male subjects (54%). Most (86%) were Mycobacterium avium/intracellulare cases; 68 (6%) were Mycobacterium abscessus/chelonae cases. Although not statistically significant, incidence increased from 4.8/100,000 in 2007 to 5.6/100,000 in 2012 (P for trend, 0.21). Incidence increased with age, to more than 25/100,000 in patients 80 years of age or older. CONCLUSIONS This is the first population-based estimate of pulmonary NTM disease incidence in a region within the United States. In Oregon, disease incidence rose slightly during 2007 to 2012, and although more common in female individuals overall, disease was more common among male individuals less than 60 years of age.

Human papillomavirus genotypes in high grade cervical lesions in the United States

BACKGROUND Two vaccines protect against human papillomaviruses (HPV) 16 and 18, which cause 70% of cervical cancer and 50% of cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+). Monitoring HPV types in CIN2+ may be used to assess HPV vaccine impact. METHODS As part of a multisite vaccine impact monitoring project (HPV-IMPACT), biopsy specimens used to diagnose CIN2+ were obtained for HPV DNA typing for women aged 18-39 years. RESULTS Among 4,121 CIN2+ cases reported during 2008-2009 in 18- to 39-year-old women 3058 (74.2%) were tested; 96% were HPV DNA positive. HPV 16 was most common (49.1%), followed by HPV 31 (10.4%) and HPV 52 (9.7%). HPV 18 prevalence was 5.5% overall. Proportion of CIN2+ cases associated with HPV 16/18 was highest (56.3%) in 25- to 29-year-old women. HPV 16/18-associated lesions were less common in non-Hispanic blacks (41.9%) and Hispanics (46.3%) compared with non-Hispanic whites (59.1%) (P < .0001); the difference remained significant when adjusted for covariates. Compared to non-Hispanic whites, HPV 35 and 58 were significantly more common in non-Hispanic blacks (14.5% vs 4.2%; 12.3% vs 3.4%) and HPV 45 was higher in Hispanics (3.7% vs 1.5%). CONCLUSIONS Age and racial/ethnic differences in HPV type distribution may have implications for vaccine impact and should be considered in monitoring trends.

The HPV vaccine impact monitoring project (HPV-IMPACT): assessing early evidence of vaccination impact on HPV-associated cervical cancer precursor lesions

The following paper describes a collaboration between the Centers for Disease Control and Prevention and five Emerging Infections Program sites to develop a comprehensive population-based approach to monitoring human papillomavirus (HPV) vaccine impact on cervical cancer precursors and associated HPV genotypes. The process of establishing this novel monitoring system is described, and development details such as enumeration of sources for reporting cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ, approaches to case ascertainment, electronic reporting, and HPV typing are outlined. Implementation of a feasible and sustainable surveillance system for HPV-associated cervical precancers will enable evaluation of the direct impact of HPV vaccination.

Population-Based Trends in High-Grade Cervical Lesions in the Early Human Papillomavirus Vaccine Era in the United States

Cervical intraepithelial neoplasia grade 2, 3, and adenocarcinoma in situ (CIN2+) lesions can be monitored as early indicators of human papillomavirus (HPV) vaccine impact. Changes to screening utilization will affect observed reductions in CIN2+ rates and complicate the interpretation of vaccine impact.

Emergence of increased azithromycin resistance during unsuccessful treatment of Neisseria gonorrhoeae infection with azithromycin (Portland, OR, 2011).

We describe the emergence of an azithromycin-resistant Neisseria gonorrhoeae variant in a man from Portland, Oregon, during sole treatment with 2 g azithromycin. This report highlights the ease with which gonococcal macrolide resistance can emerge, the threat of multidrug resistant N. gonorrhoeae, and the need for adherence to Centers for Disease Control and Prevention treatment guidelines.

HPV Type Attribution in High-Grade Cervical Lesions: Assessing the Potential Benefits of Vaccines in a Population-Based Evaluation in the United States

Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden. Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected. Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001). Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities. Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR.

Mycobacterium chelonae Facial Infections Following Injection of Dermal Filler

UNLABELLED A cluster of 3 facial Mycobacterium chelonae infections occurred after cosmetic dermal filler injections at a plastic surgery clinic. Pulsed-field gel electrophoresis showed that M chelonae isolated from the clinic tap water were identical to the patient wound isolates. Review of injection procedures identified application of nonsterile ice to the skin prior to injection as a possible source of M chelonae. Surveys of regional laboratories and a national plastic surgery listserv identified no other cases related to the injection of this brand of dermal filler. This is the first report of cutaneous M chelonae infections following the injection of dermal fillers. It adds to a growing body of literature on postinjection M chelonae infections and reinforces the importance of optimal skin disinfection steps prior to percutaneous procedures. LEVEL OF EVIDENCE 5.

Using Diagnostic Codes to Screen for Intimate Partner Violence in Oregon Emergency Departments and Hospitals

Objectives. Many of the 2.5 million Americans assaulted annually by intimate partners seek medical care. This project evaluated diagnostic codes indicative of intimate partner violence (IPV) in Oregon hospital and emergency department (ED) records to determine predictive value positive (PVP), sensitivity, and usefulness in routine surveillance. Statewide incidence of care for IPV was calculated and victims and episodes characterized. Methods. The study was a review of medical records assigned ≥1 diagnostic codes thought predictive of IPV. Sensitivity was estimated by comparing the number of confirmed victims identified with the number predicted by statewide telephone survey. Patients were aged ≥2 years, treated in any of 58 EDs or hospitals in Oregon during 2000, and discharged with one of three primary or 12 provisional codes suggestive of IPV. Outcome measures were number of victims detected, PPV and sensitivity of codes for detection of IPV, and description of victims. Results. Of 58 hospitals, 52 (90%) provided records. Case finding using primary codes identified 639 victims, 23% of all estimated female victims seen in EDs or hospitalized statewide. PVP was 94% (639/677). Provisional codes increased sensitivity (51%) but reduced PVP (50%). Highest incidence occurred in women aged 20–39 years, and those who were black. Hospitalizations were highest among women aged

Monitoring Effect of Human Papillomavirus Vaccines in US Population, Emerging Infections Program, 2008–2012

50 years, black people, or those with comorbid illness. Conclusions. Three diagnostic codes used for case finding detect approximately one-quarter of ED- and hospital-treated victims, complement surveys, and facilitate description of injured victims.