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.

BACKGROUND: Competent leadership and management are imperative for delivering quality laboratory services; however, few laboratory managers receive job-specific training in organisational management and leadership. OBJECTIVE: To develop and evaluate participants' competencies in organisational leadership and management as measured through learner and laboratory quality improvement assessments. METHODS: This professional development programme employed a mentored, blended learning approach, utilising in-person didactic and online training, with the practical application of a capstone project in the laboratories. Programme impact was evaluated through a series of pre- and post-laboartory assessments using the Stepwise Laboratory Improvement Process Towards Accreditation checklist, as well as learner-competency assessments through online quizzes and discussions. RESULTS: From 2016 to 2018, 31 managers and quality officers from 16 individual laboratories graduated from the programme having completed capstone projects addressing areas in the entire laboratory testing process. Laboratories increased their compliance with the International Organization for Standardization 15189 standard and all but two laboratories significantly increased their accreditation scores. Two laboratories gained three stars, two laboratories gained two stars, and five laboratories gained one star. Five laboratories subsequently achieved International Organization for Standardization 15189 accreditation in 2019. CONCLUSION: This programme taught leadership theory to laboratory managers and allowed them to implement leadership and management practices in the laboratory setting. Programmes such as this complement existing laboratory quality management training programmes such as Strengthening Laboratory Management Toward Accreditation.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection. Men who have sex with men (MSM) and transgender women (TGW) are at high risk for anal HPV infection and subsequent anal cancer. This study assessed the association of partner discordances with prevalent high-risk anal HPV (HRAHPV) among MSM and TGW. METHODS: Participants were enrolled in the cross-sectional young men's HPV study of gay, bisexual, and other MSM, and TGW, aged 18 to 26 years, from 2 cities. Participants completed a confidential standardized computer-assisted interview and provided self-collected anal swabs for type-specific HPV DNA testing. Multivariate analyses were conducted for 3 discordances of interest (i.e., partner age, race/ethnicity, and concurrent partner) to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Eight hundred sixty-two participants were included for partner race/ethnicity discordance, 601 for partner age discordance, and 581 for concurrent partner analysis. Most reported being older than 21 years, cisgender male, and gay. Adjusted odds of HRAHPV were not significantly increased among participants reporting partner age discrepancy >10 years (aOR, 0.89; 95% CI, 0.51-1.56), partner race/ethnicity discordance (aOR, 0.88; CI, 0.62-1.24), or partner with concurrent partners (aOR, 0.85; 95% CI, 0.50-1.42), compared with those who did not. CONCLUSIONS: This analysis did not identify any partner discordances associated with HRAHPV. Because HPV infection can persist for years, sexual mixing patterns with early partners might be more relevant than the most recent sex partner. Prevalence of HRAHPV was high and could be preventable by preexposure vaccination, as recommended for everyone through age 26 years including MSM and TGW.

Background: The first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination. Methods: For this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types. Results: Four hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). (p < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. (p < 0.001). Conclusions: A substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time.

BACKGROUND: Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet few mail-based HPV self-testing programs have been implemented in the United States. We report the results of a pilot study of a mail-based program, the Health Outcomes through Motivation and Education Project. METHODS: In 2015 to 2016, we recruited 103 women from Appalachian Ohio who were aged 30 to 65 years and had not received a Papanicolaou (Pap) test in at least 3 years. Women were mailed an HPV self-test and randomized to receive either (a) self-test instructions developed by the device manufacturer and a standard information brochure about cervical cancer (control group) or (b) self-test instructions developed by the Health Outcomes through Motivation and Education Project and a photo story information brochure about cervical cancer (intervention group). Logistic regression compared study arms on HPV self-test return and receipt of a Pap test. RESULTS: Overall, 80 (78%) women returned their HPV self-test. Return was similar among the intervention and control groups (78% vs. 77%; odds ratio, 1.09; 95% confidence interval, 0.43-2.76). Among returners, 26% had an oncogenic HPV type detected in their sample. Women who returned their self-test reported high levels of satisfaction and positive experiences with the self-testing process. Few women overall received a Pap test (11%), and Pap testing was similar among the intervention and control groups (14% vs. 8%; odds ratio, 1.91; 95% confidence interval, 0.52-6.97). CONCLUSIONS: Mail-based HPV self-testing programs are a potentially promising strategy for reaching underscreened women in Appalachia. Efforts are needed to better understand how to optimize the success of such programs.

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.

BACKGROUND: Human papillomavirus (HPV) prevalence is high among men who have sex with men (MSM), yet little is known about HPV among transgender women (TGW). We assessed HPV prevalence and knowledge among TGW compared with MSM. METHODS: We enrolled TGW and MSM aged 18 to 26 years from clinics in Chicago and Los Angeles during 2012 to 2014. Participants self-reported gender identity, HIV status, HPV knowledge, and vaccination status. Self-collected anal and oral specimens were tested for HPV DNA (37 types); serum was tested for HPV antibodies (4 vaccine types). Prevalence among unvaccinated TGW and MSM was compared using prevalence ratios (PRs) and 95% confidence intervals (CIs). Participants without DNA or serologic evidence of HPV were considered naive. RESULTS: Among 1033 participants, 49 were TGW. Among 44 TGW and 855 MSM who were unvaccinated, any HPV DNA was detected in anal specimens from 39 (88.6%) TGW and 606 (70.9%) MSM (PR, 1.3; 95% CI, 1.1-1.4), and oral specimens from 4 (9.1%) TGW and 81 (9.5%) MSM (PR, 1.0; 95% CI, 0.4-2.5). Antibodies were detected among 37 (84.1%) TGW and 467 (54.6%) MSM (PR, 1.5; 95% CI, 1.3-1.8). Most participants were naive to 1 or more HPV vaccine type/s, including 29 (65.9%) TGW and 775 (90.6%) MSM (PR, 0.7; 95% CI, 0.6-0.9). Most TGW (55.1%) had never heard of HPV vaccine. CONCLUSIONS: Among TGW, HPV prevalence was high and knowledge was low. Most were still naive to 1 or more HPV vaccine type. Although vaccination ideally occurs prior to exposure, findings support existing national recommendations to vaccinate TGW and MSM, and suggest additional outreach might increase vaccination.

BACKGROUND: Human papillomavirus (HPV) vaccine has been recommended in the United States since 2006 for routine vaccination of girls at age 11-12years and through age 26years for women not previously vaccinated. Changes in vaccine-type HPV (VT) prevalence can be used to evaluate vaccine impact, including herd effects. METHODS: We determined type-specific HPV in cytology specimens from women aged 20-29years screened for cervical cancer at Kaiser Permanente Northwest in 2007 and in two vaccine era periods: 2012-2013 and 2015-2016. Detection and typing used L1 consensus PCR with hybridization for 37 types, including quadrivalent vaccine types (HPV 6/11/16/18). RESULTS: Among 20-24year-olds in 2012-2013 and 2015-2016, 44% and 64% had a history of >/=1-dose vaccination. VT prevalence decreased from 13.1% in 2007 to 2.9% in 2015-2016 (prevalence ratio [PR]=0.22; 95% confidence interval [CI] 0.17-0.29). HPV 31 prevalence was also lower in the vaccine periods compared with 2007. VT prevalence in 2015-2016 among 20-24year-olds was lower in both vaccinated, 1.3% (PR=0.10; 95% CI 0.06-0.16), and unvaccinated women, 5.8% (PR=0.45; 95% CI 0.33-0.61). Among 25-29year-olds, 21% and 32% had a history of >/=1-dose vaccination. VT prevalence decreased from 8.1% in 2007 to 5.0% in 2015-2016 (PR=0.62; 95% CI 0.50-0.78). Non-VT high risk prevalence was higher in the vaccine periods compared with the pre-vaccine era in both age groups, however, not in 2015-2016 compared with 2012-2013. CONCLUSION: Within 9-10years of vaccine introduction, VT prevalence decreased 78% among 20-24year-olds and 38% in 25-29year-olds. There were declines in both vaccinated and unvaccinated women, showing evidence of direct and herd protection.

Objectives: The role of HPV in oral cavity cancers was investigated using two markers of viral exposure. Materials and methods: HPV DNA and p16 INK4a expression were evaluated in tumor tissue from a U.S. population-based sample of 122 invasive oral cavity cancer cases. Results: HPV DNA was detected in 38 of 122 (31%) oral cavity tumors. Seven genotypes were detected including HPV 16, which was found in 22% of tumors. p16 INK4a was expressed in 30% of tumors and was poorly correlated with HPV DNA detection (Kappa &lt;0.1). Joint positivity for HPV 16 and/or 18 and p16 INK4a was observed in only 7% of cases. When comparing cases diagnosed in 1993–1999 and in 2000–2004, positivity for HPV DNA 16/18 increased from 19% to 39% (p = 0.02) and joint HPV 16/18 – p16 INK4a positivity increased from 0% to 12% (p = 0.01). For gingival tumors, HPV 16 and/or 18 positivity was 67% compared to 11–38% for other sites (p = 0.02); joint HPV 16/18 – p16 INK4a positivity was 33% compared to 0–8% for other sites (p = 0.01). The association of HPV with gingival tumors and more recent diagnosis period remained after adjustment for age and stage (p &lt; 0.05). Neither HPV DNA nor p16 INK4a were associated with overall survival. Conclusions: Based on both HPV DNA and p16 INK4a , HPV is etiologically linked to a limited subset of oral cavity cancers. However, the role of HPV in oral cavity cancer may vary widely by subsite and may have increased over time, similar to trends observed for oropharyngeal cancer. © 2019 Elsevier Ltd

INTRODUCTION: The 2006 introduction of human papillomavirus vaccine targeted against genotypes 6, 11, 16, and 18 should result in decreased cervical dysplasia in vaccinated women. However, new cervical cancer guidelines to increase screening intervals complicate interpretation of trends. The hypothesis is that cervical dysplasia would decrease only in young vaccine-eligible women, and not older women. METHODS: The authors identified Davidson County, Tennessee, women aged 18-39 years with cervical intraepithelial neoplasia (CIN) grade 2 or greater and adenocarcinoma in situ, denoted as CIN2+, through pathology reports from laboratories serving this population. Biopsy specimens for human papillomavirus genotyping were collected. Trends in CIN2+ rates and associated human papillomavirus genotypes, 2008 through 2013, were examined. RESULTS: The authors identified 2,031 women with CIN2+. Rates of CIN2+ fell from 188.9 to 58.7 per 100,000 women aged 18-20 years (annual percentage change= -24.2, 95% CI= -41.4, -2.1) and from 495.6 to 332.4 per 100,000 women aged 21-24 years (annual percentage change= -10.2%, 95% CI= -16.3, -3.4). There was no significant change in CIN2+ rates for women aged 25-29 or 30-39 years. In biopsy specimens from 1,319 of 2,031 (65%) women, at least one human papillomavirus genotype was identified in 1,270 (96%). The prevalence of at least one of four vaccine human papillomavirus genotypes (6, 11, 16, and 18) declined from 59% in 2008 to 52% in 2013 (p=0.003). CONCLUSIONS: Diagnosis of CIN2+ decreased in women aged 18-24 years, but not in older women. Both changes in screening and human papillomavirus vaccination could have contributed to the decline of CIN2+ in young women.

BACKGROUND: Men who have sex with men (MSM) are at risk for cancers attributable to human papillomavirus (HPV), including oropharyngeal cancer. HPV vaccination is recommended for U.S. MSM through age 26 years. Oral HPV infection is associated with oropharyngeal cancer. We determined oral HPV prevalence and risk factors among young MSM. METHODS: The Young Men's HPV study enrolled MSM aged 18-26 years from clinics in Chicago and Los Angeles during 2012-2014. Participants self-reported demographics, sexual behaviors, vaccination and HIV status. Self-collected oral rinse specimens were tested for HPV DNA (37 types) by L1-consensus PCR. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for risk factors associated with oral HPV among participants not previously vaccinated. RESULTS: Oral HPV was detected in 87/922 (9.4%); 9-valent vaccine (9vHPV) types were detected in 37/922 (4.0%). Among HIV-positive participants, 17/88 (19.3%) had oral HPV detected. Oral HPV was more prevalent among those reporting first sex at age </=18 years (aPR:2.44; CI:1.16-5.12); HIV infection (aPR:1.99; CI:1.14-3.48); >5 sex partners within the past month (aPR:1.93; CI:1.13-3.31); performing oral sex on >5 partners within the last 3 months (aPR:1.87; CI:1.12-3.13); and having >5 male sex partners within the last 3 months (aPR:1.76; CI: 1.08-2.87). Only 454/922 (49.2%) were aware HPV can cause oropharyngeal cancers. CONCLUSIONS: Many oral HPV infections were with types targeted by vaccination. Oral HPV infections were significantly associated with HIV and sexual behaviors. Fewer than half of participants were aware HPV could cause oropharyngeal cancer.

BACKGROUND: Men who have sex with men (MSM) are at risk for cancers attributable to human papillomavirus (HPV), including oropharyngeal cancer. HPV vaccination is recommended for U.S. MSM through age 26 years. Oral HPV infection is associated with oropharyngeal cancer. We determined oral HPV prevalence and risk factors among young MSM. METHODS: The Young Men's HPV study enrolled MSM aged 18-26 years from clinics in Chicago and Los Angeles during 2012-2014. Participants self-reported demographics, sexual behaviors, vaccination and HIV status. Self-collected oral rinse specimens were tested for HPV DNA (37 types) by L1-consensus PCR. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for risk factors associated with oral HPV among participants not previously vaccinated. RESULTS: Oral HPV was detected in 87/922 (9.4%); 9-valent vaccine (9vHPV) types were detected in 37/922 (4.0%). Among HIV-positive participants, 17/88 (19.3%) had oral HPV detected. Oral HPV was more prevalent among those reporting first sex at age </=18 years (aPR:2.44; CI:1.16-5.12); HIV infection (aPR:1.99; CI:1.14-3.48); >5 sex partners within the past month (aPR:1.93; CI:1.13-3.31); performing oral sex on >5 partners within the last 3 months (aPR:1.87; CI:1.12-3.13); and having >5 male sex partners within the last 3 months (aPR:1.76; CI: 1.08-2.87). Only 454/922 (49.2%) were aware HPV can cause oropharyngeal cancers. CONCLUSIONS: Many oral HPV infections were with types targeted by vaccination. Oral HPV infections were significantly associated with HIV and sexual behaviors. Fewer than half of participants were aware HPV could cause oropharyngeal cancer.

Background: Differences in human papillomavirus (HPV) prevalence among males and females have been reported. Using the 2013-2014 National Health and Nutrition Examination Survey, we evaluated sex differences in prevalence overall and by demographic and sexual behavior characteristics. Methods: Self-collected penile and cervicovaginal swabs from participants ages 14-59 were tested for HPV DNA. Prevalences of any HPV and high-risk (HR-)HPV were estimated for sexually experienced males and females. Overall and in models stratified by demographic characteristics and behaviors, prevalence was compared in males to females using prevalence ratios (PR). Results: Overall, males had higher prevalences than females of any HPV (PR: 1.14, 95% confidence interval [CI]: 1.03-1.27) and HR-HPV (PR: 1.24, 95% CI: 1.07-1.43). Prevalences were lower among males than females at ages 14-19 and higher at ages 40-49 and 50-59. Sex differences in models stratified by race/ethnicity, poverty, sexual behaviors, and smoking were observed. After adjusting for lifetime sex partners, most sex differences were attenuated, but males had lower prevalences at ages 14-19 and 20-24 and higher HR-HPV prevalence among non-Hispanic blacks. Conclusions: Any HPV and HR-HPV prevalences were significantly higher in males; sex differences varied by age group and race/ethnicity. Lifetime partners explained many of the differences by sex.

Background: Human papillomavirus (HPV) vaccine was recommended in 2006 for routine vaccination of US females aged 11-12 years. Most vaccine used through 2014 was quadrivalent vaccine (4vHPV), which prevents HPV-6, -11, -16, and -18 infection. To evaluate vaccine impact, we measured HPV prevalence in the National Health and Nutrition Examination Survey (NHANES). Methods: We analyzed HPV DNA types detected in self-collected cervicovaginal specimens and demographic, sexual behavior, and self-reported vaccination data from females 14-34 years old. We estimated HPV prevalence in the prevaccine (2003-2006) and vaccine eras (2007-2010 and 2011-2014). Results: Among 14- to 19-year-olds, 4vHPV-type prevalence decreased from 11.5% (95% confidence interval [CI], 9.1%-14.4%) in 2003-2006 to 3.3% (95% CI, 1.9%-5.8%) in 2011-2014, when ≥1-dose coverage was 55%. Among 20- to 24-year-olds, prevalence decreased from 18.5% (95% CI, 14.9%-22.8%) in 2003-2006 to 7.2% (95% CI, 4.7%-11.1%) in 2011-2014, when ≥1-dose coverage was 43%. Compared to 2003-2006, 4vHPV prevalence in sexually active 14- to 24-year-olds in 2011-2014 decreased 89% among those vaccinated and 34% among those unvaccinated. Vaccine effectiveness was 83%. Conclusions: Within 8 years of vaccine introduction, 4vHPV-type prevalence decreased 71% among 14- to 19-year-olds and 61% among 20- to 24-year-olds. Estimated vaccine effectiveness was high. The decrease in 4vHPV-type prevalence among unvaccinated females suggests herd protection.

Prevalence of human papillomavirus (HPV) infections was assessed among 1033 young men who have sex with men (MSM) aged 18-26 years. HPV (any type) was detected in 742 (71.8%) anal specimens and 101 (9.8%) oral specimens. Although HPV was detected in specimens from both anatomical sites in 83 (8.0%) participants, type-specific concordance for at least one HPV type was found in only 35 (3.4%) participants. HIV and smoking were associated with higher prevalence at both sites and frequency of concordant types. Coinfections of identical HPV types were rare, suggesting independent infection events and/or different modes of clearance.

BACKGROUND: We report the first nationally representative prevalence data on genital human papillomavirus (HPV) in males in the United States, using findings from the National Health and Nutrition Examination Surveys, 2013-2014. METHODS: Using penile swabs from males aged 14-59 years, we estimated the HPV DNA prevalence and prevalence ratios (PRs) with respect to sexual behaviors and demographic characteristics. RESULTS: The prevalence of any HPV was 42.2% (95% confidence interval [CI], 38.3%-46.1%) and of high-risk (HR) HPV was 23.4% (95% CI, 21.3%-25.6%). Prevalence of any HPV was 12.5% in 14-19 year olds and was higher in older age groups, through ages 25-29 years, and then similar through age 59 years. After adjustment for age and race, any HPV prevalence was associated with lifetime number of sex partners (>/=15 vs 1-2; PR, 3.27; 95% CI, 2.12-5.02) and past-year number of sex partners (>/=2 vs 0; PR, 1.26; 95% CI, 1.09-1.46). Comparisons of consecutively older age groups revealed that the prevalence of quadrivalent HPV vaccine types (4vHPV), types 6, 11, 16, and 18, was significantly higher only between ages 25-29 and 20-24 years (PR, 2.79; 95% CI, 1.31-5.96), whereas the prevalence of other HPV types was significantly higher only between ages 20-24 and 14-19 years (PR, 3.39; 95% CI, 2.49-4.61). CONCLUSIONS: Overall, 42.2% of US males aged 14-59 years have detectable genital HPV infections. Differences in the age-specific prevalence of 4vHPV types and non-4vHPV types suggest that the vaccination program has had an impact on the prevalence of HPV types 6, 11, 16, and 18 among males.

We examined p16 expression in tumors from a population-based sample of laryngeal cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV DNA. Overall, p16 expression was observed in laryngeal tissue from 8 of 101 (7.9%) cases. p16 expression was observed in 2 of 16 (12.5%) cases previously determined to be HPV DNA positive. The two cases dually positive for p16 and HPV DNA were non-keratinizing SCC and papillary SCC tumors that were positive for genotypes 18 and 35/89, respectively. Positivity for p16 and/or HPV DNA was not associated with 5-year survival (log-rank p value=0.55). Our findings support a limited role of HPV in laryngeal carcinogenesis. p16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival.

We designed a universal HPV typing assay based on target enrichment and whole genome sequencing (eWGS). The RNA bait included 23,941 probes targeting 191 HPV types and 12 targeting beta-globin as control. We used Agilent SureSelect XT2 protocol for library preparation, Illumina HiSeq 2500 for sequencing and CLC genomics workbench for sequence analysis. Mapping stringency for type assignment was determined based on 8 (6 HPV-positive and 2 HPV negative) control samples. Using the optimal mapping conditions, types were assigned to 24 blinded samples. eWGS results were 100% concordant with Linear Array (LA) genotyping results for 9 plasmid samples and fully or partially concordant for 9 of the 15 cervical-vaginal samples, with 95.83% overall-type specific concordance for LA genotyping. eWGS identified 7 HPV types not included in the LA genotyping. Since this method does not involve degenerate primers targeting HPV genomic regions, PCR bias in genotype detection is minimized. With further refinements aimed at reducing cost and increasing throughput, this first application of eWGS for universal HPV typing could be a useful method to elucidate HPV epidemiology.

Before any vaccine introduction, overall DNA prevalence of any 9-valent human papillomavirus (9vHPV) types, HPV 31/33/45/52/58, and HPV 16/18 was 16.0%, 9.5%, and 6.2%, respectively, among female participants in National Health and Nutrition Examination Survey. Non-Hispanic black females were more likely to have infection with HPV 31/33/45/52/58, but not HPV 16/18, compared to non-Hispanic white females.

BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are at high risk for HPV; vaccination is recommended for U.S. males, including MSM through age 26. We assessed evidence of HPV among vaccine-eligible MSM and transgender women to monitor vaccine impact. METHODS: During 2012-14, MSM age 18-26 at selected clinics completed a computer-assisted self-interview regarding sexual behavior, HIV status, and vaccinations. Self-collected anal swab and oral rinse specimens were tested for HPV DNA (37 types) by L1 consensus PCR; serum was tested for HPV antibodies (4 types) by multiplexed VLP-based IgG direct ELISA. RESULTS: Among 922 vaccine-eligible participants, mean age was 23, and mean number of lifetime sex partners was 37. Among 834 without HIV, any anal HPV was detected in 69.4% and any oral HPV in 8.4%, yet only 8.5% had evidence of exposure to all quadrivalent vaccine types. In multivariate analysis, HPV prevalence varied significantly (p<0.05) by HIV status, sexual orientation, and lifetime sex partners, but not race/ethnicity. DISCUSSION: Most young MSM lacked evidence of current or past infection with all vaccine-type HPV, suggesting they could benefit from vaccination. Vaccination impact among MSM may be assessed by monitoring HPV prevalence, including in self-collected specimens.

BACKGROUND: Since mid-2006, human papillomavirus (HPV) vaccination has been recommended for females aged 11 to 12 years and through 26 years if not previously vaccinated. METHODS: HPV DNA prevalence was analyzed in cervicovaginal specimens from females aged 14 to 34 years in NHANES in the prevaccine era (2003-2006) and 4 years of the vaccine era (2009-2012) according to age group. Prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV-6, -11, -16, and -18) and other HPV type categories were compared between eras. Prevalence among sexually active females aged 14 to 24 years was also analyzed according to vaccination history. RESULTS: Between the prevacccine and vaccine eras, 4vHPV type prevalence declined from 11.5% to 4.3% (adjusted prevalence ratio [aPR]: 0.36 [95% confidence interval (CI): 0.21-0.61]) among females aged 14 to 19 years and from 18.5% to 12.1% (aPR: 0.66 [95% CI: 0.47-0.93]) among females aged 20 to 24 years. There was no decrease in 4vHPV type prevalence in older age groups. Within the vaccine era, among sexually active females aged 14 to 24 years, 4vHPV type prevalence was lower in vaccinated (≥1 dose) compared with unvaccinated females: 2.1% vs 16.9% (aPR: 0.11 [95% CI: 0.05-0.24]). There were no statistically significant changes in other HPV type categories that indicate cross-protection. CONCLUSIONS: Within 6 years of vaccine introduction, there was a 64% decrease in 4vHPV type prevalence among females aged 14 to 19 years and a 34% decrease among those aged 20 to 24 years. This finding extends previous observations of population impact in the United States and demonstrates the first national evidence of impact among females in their 20s.

BACKGROUND: The presence of human papillomavirus (HPV) DNA in oropharyngeal squamous cell cancer (OPSCC) tissue appears to be a strong predictor of improved prognosis, but this observation has not been explored in a population-based sample with generalisable findings. METHODS: Follow-up data from a large sample of OPSCC patients identified through six population-based cancer registries in the United States of America (USA) were used to characterise the association of tumour HPV status with survival. RESULTS: HPV DNA was detected in tumour tissue from 71% (378 in 529) of the OPSCC patients. A total of 65% of patients with HPV16-associated tumours survived 5 years compared to 46% of patients with other HPV types and 28% of patients with HPV-negative tumours (p log-rank test <0.0001). The OPSCC patients with detectable HPV16 DNA had a 62% reduced hazard of death at 5 years, and patients with other HPV types had a 42% reduced hazard of death at 5 years compared to HPV-negative patients. Compared to non-Hispanic Whites, Blacks with OPSCC had a 2.6-fold greater risk of death at 5 years after adjustment for HPV status and other prognostic variables. Both surgery and radiation therapy were associated with a reduced 5-year risk of death, but no evidence was found for an interaction between HPV status and radiotherapy or surgery on survival time. CONCLUSIONS: Data from this US study suggest that HPV16-positive OPSCC patients survive longer than HPV-negative patients regardless of treatment, highlighting the prognostic importance of HPV status for this malignancy. Optimal treatment regimens for OPSCC could be tailored to each patient's HPV status and prognostic profile.

In 2007, five Emerging Infections Program (EIP) sites were funded to determine the feasibility of establishing a population-based surveillance system for monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive cervical lesions. The project involved active population-based surveillance of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as well as associated HPV types in women >18 years of age residing in defined catchment areas; collecting relevant clinical information and detailed HPV vaccination histories for women 18-39 years of age; and estimating the annual rate of cervical cancer screening among the catchment area population. The first few years of the project provided key information, including data on HPV type distribution, before expected effect of vaccine introduction. The project's success exemplifies the flexibility of EIP's network to expand core activities to include emerging surveillance needs beyond acute infectious diseases. Project results contribute key information regarding the impact of HPV vaccination in the United States.

BACKGROUND: Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. CONCLUSIONS: Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.

In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prevention established a field laboratory in Sierra Leone in response to the ongoing Ebola virus outbreak. Through March 2015, this laboratory tested >12 000 specimens from throughout Sierra Leone. We describe the organization and procedures of the laboratory located in Bo, Sierra Leone.

BACKGROUND: In the U.S., HPV vaccine is recommended for 11 and 12 year olds, and for young adults not previously vaccinated. Early vaccine impact can be measured by reductions in vaccine type (VT) HPV prevalence. METHODS: Consecutive residual cervical specimens were retained from women aged 20-29 years in Kaiser Permanente Northwest in 2007, 2012, and 2013. HPV genotypes were determined using L1 consensus PCR with type-specific hybridization to detect 37 types, including VT HPV (HPV type 6, 11, 16, 18). We compared HPV prevalence in 2007 and 2012-2013, and we evaluated predictors of VT and any HPV prevalence in 2012-2013. RESULTS: In 2012-2013, 31.9% of 4181 women had initiated HPV vaccination. VT HPV decreased from 10.6% in 2007, to 6.2% in 2012-2013 (p<0.001). In 2012-2013, VT HPV was significantly lower among those who initiated vaccination <19 years (adjusted prevalence ratio (aPR) 0.1, 95% Confidence Interval (CI) 0.1, 0.3) compared to those who were not vaccinated, and higher among those who had chlamydia, HIV or pregnancy testing in the last year compared to those who did not have testing (aPR 1.4, 95% CI 1.1, 1.8). CONCLUSIONS: Reduction in VT HPV was found in young women in an integrated healthcare delivery system within 6 years of vaccine introduction indicating early HPV vaccine impact.

BACKGROUND: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. METHODS: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. RESULTS: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. CONCLUSIONS: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.

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.

PURPOSE: Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S. METHODS: The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993-2004 within the catchment area of three U.S. SEER cancer registries. RESULTS: HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07-7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status. CONCLUSIONS: HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men.

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 an investigational 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 aged 21-39 years residing in 5 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 2008-2011, 5,498/6,306 (87.2%) of 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%-52.4% among those aged 21-34 years, and significantly declined in 35-39 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+ were attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared to 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 reduce racial/ethnic differences in high-grade cervical lesions.