Lauri E. Markowitz

Annual Report to the Nation on the Status of Cancer, 1975–2009, Featuring the Burden and Trends in Human Papillomavirus (HPV)–Associated Cancers and HPV Vaccination Coverage Levels

Background The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year’s report includes incidence trends for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years). Methods Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mortality were obtained from the CDC. Long- (1975/1992–2009) and short-term (2000–2009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys. Results Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] = 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI = 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI = 13.9% to 27.9%] and Mississippi [95% CI = 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest. Conclusions The overall trends in declining cancer death rates continue. However, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV-associated cancers, including efforts to increase vaccination coverage.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years — United States, 2014

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive vaccines to prevent diseases, including human papillomavirus (HPV)-associated cancers, pertussis, and meningococcal disease (1). To assess vaccination coverage among adolescents in the United States, CDC analyzed data collected regarding 21,875 adolescents through the 2015 National Immunization Survey-Teen (NIS-Teen).* During 2014-2015, coverage among adolescents aged 13-17 years increased for each HPV vaccine dose among males, including ≥1 HPV vaccine dose (from 41.7% to 49.8%), and increased modestly for ≥1 HPV vaccine dose among females (from 60.0% to 62.8%) and ≥1 quadrivalent meningococcal conjugate vaccine (MenACWY) dose (from 79.3% to 81.3%). Coverage with ≥1 HPV vaccine dose was higher among adolescents living in households below the poverty level, compared with adolescents in households at or above the poverty level.(†) HPV vaccination coverage (≥1, ≥2, or ≥3 doses) increased in 28 states/local areas among males and in seven states among females. Despite limited progress, HPV vaccination coverage remained lower than MenACWY and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) coverage, indicating continued missed opportunities for HPV-associated cancer prevention.

Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine

CONTEXT In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years. OBJECTIVE To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV. DESIGN, SETTING, AND PARTICIPANTS Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting. MAIN OUTCOME MEASURES Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates. RESULTS VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barré syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods. CONCLUSIONS Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system.

Reduction in Human Papillomavirus (HPV) Prevalence Among Young Women Following HPV Vaccine Introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010

BACKGROUND Human papillomavirus (HPV) vaccination was introduced into the routine immunization schedule in the United States in late 2006 for females aged 11 or 12 years, with catch-up vaccination recommended for those aged 13-26 years. In 2010, 3-dose vaccine coverage was only 32% among 13-17 year-olds. Reduction in the prevalence of HPV types targeted by the quadrivalent vaccine (HPV-6, -11, -16, and -18) will be one of the first measures of vaccine impact. METHODS We analyzed HPV prevalence data from the vaccine era (2007-2010) and the prevaccine era (2003-2006) that were collected during National Health and Nutrition Examination Surveys. HPV prevalence was determined by the Linear Array HPV Assay in cervicovaginal swab samples from females aged 14-59 years; 4150 provided samples in 2003-2006, and 4253 provided samples in 2007-2010. RESULTS Among females aged 14-19 years, the vaccine-type HPV prevalence (HPV-6, -11, -16, or -18) decreased from 11.5% (95% confidence interval [CI], 9.2-14.4) in 2003-2006 to 5.1% (95% CI, 3.8-6.6) in 2007-2010, a decline of 56% (95% CI, 38-69). Among other age groups, the prevalence did not differ significantly between the 2 time periods (P > .05). The vaccine effectiveness of at least 1 dose was 82% (95% CI, 53-93). CONCLUSIONS Within 4 years of vaccine introduction, the vaccine-type HPV prevalence decreased among females aged 14-19 years despite low vaccine uptake. The estimated vaccine effectiveness was high.

The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health

Objectives: Bacterial vaginosis (BV), a disturbance of vaginal microflora, is a common cause of vaginal symptoms and is associated with an increased risk of acquisition of sexually transmitted infections, HIV, and with adverse pregnancy outcomes. We determined prevalence and associations with BV among a representative sample of women of reproductive age in the United States. Study Design: Women aged 14–49 years participating in the National Health and Nutrition Examination Survey 2001–2004 were asked to submit a self-collected vaginal swab for Gram staining. BV, determined using Nugent’s score, was defined as a score of 7–10. Results: The prevalence of BV was 29.2% (95% confidence interval 27.2%–31.3%) corresponding to 21 million women with BV; only 15.7% of the women with BV reported vaginal symptoms. Prevalence was 51.4% among non-Hispanic blacks, 31.9% among Mexican Americans, and 23.2% among non-Hispanic whites (P <0.01 for each comparison). Although BV was also associated with poverty (P <0.01), smoking (P <0.05), increasing body mass index (&khgr;2P <0.0001 for trend), and having had a female sex partner (P <0.005), in the multivariate model, BV only remained positively associated with race/ethnicity, increasing lifetime sex partners (&khgr;2P <0.001 for trend), increasing douching frequency (&khgr;2P for trend <0.001), low educational attainment (P <0.01), and inversely associated with current use of oral contraceptive pills (P <0.005). Conclusion: BV is a common condition; 84% of women with BV did not report symptoms. Because BV increases the risk of acquiring sexually transmitted infections, BV could contribute to racial disparities in these infections.

Prevalence of Sexually Transmitted Infections Among Female Adolescents Aged 14 to 19 in the United States

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003–2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING The Canadian Institutes of Health Research.

The Prevalence of Trichomonas vaginalis Infection among Reproductive-Age Women in the United States, 2001–2004

BACKGROUND Trichomonas vaginalis infection is a common sexually transmitted protozoal infection and is associated with several adverse health outcomes, such as preterm birth, delivery of a low-birth weight infant, and facilitation of sexual transmission of human immunodeficiency virus. The annual incidence in the United States has been estimated to be 3-5 million cases. However, there are no data on the prevalence of trichomoniasis among all reproductive-age women. We estimated the prevalence of T. vaginalis infection from a nationally representative sample of women in the United States. METHODS Women aged 14-49 years who participated in the National Health and Examination Survey cycles for 2001-2004 provided self-collected vaginal swab specimens. The vaginal fluids extracted from these swabs were evaluated for the presence of T. vaginalis using polymerase chain reaction. RESULTS Overall, 3754 (81%) of 4646 women provided swab specimens. The prevalence of T. vaginalis infection was 3.1% (95% confidence interval [CI], 2.3%-4.3%); for non-Hispanic white women, it was 1.3% (95% CI, 0.7%-2.3%); for Mexican American women, it was 1.8% (95% CI, 0.9%-3.7%); and for non-Hispanic black women, it was 13.3% (95% CI, 10.0%-17.7%). Factors that remained associated with increased likelihood of T. vaginalis infection in multivariable analyses included non-Hispanic black race/ethnicity, being born in the United States, a greater number of lifetime sex partners, increasing age, lower educational level, poverty, and douching. CONCLUSIONS The prevalence of T. vaginalis infection among women in the United States was 3.1%. A significant racial disparity exists; the prevalence among non-Hispanic black women was 10.3 times higher than that among non-Hispanic white and Mexican American women. Optimal prevention and control strategies for T. vaginalis infection should be explored as a means of closing the racial disparity gaps and decreasing adverse health outcomes due to T. vaginalis infection.

Prevalence of Genital Human Papillomavirus Among Females in the United States, the National Health and Nutrition Examination Survey, 2003–2006

BACKGROUND Genital human papillomaviruses (HPV) include >40 sexually transmitted viruses. Most HPV infections do not progress to disease, but infection with certain types of HPV can cause cervical and other anogenital and oropharyngeal cancer, and other types of HPV are associated with anogenital warts. HPV vaccines prevent infection with HPV 16 and 18, which account for 70% of cases of cervical cancer, and HPV 6 and 11, which cause 90% of the cases of anogenital warts. METHODS Using data and self-collected cervicovaginal specimens from 4150 females, 14-59 years of age, from consecutive National Health and Nutrition Examination Surveys (2003-2006), we estimated the prevalence of type-specific HPV DNA and examined sociodemographic and sexual determinants. RESULTS The overall prevalence of HPV was 42.5% in females 14-59 years of age and varied significantly by age, race or ethnicity, and number of sex partners. Individual type prevalence was less than 7%, ranging from <0.5% through 6.5%. The most common type was nononcogenic HPV 62 (found in 6.5% of subjects), followed by HPV 53 and HPV 16 (4.7%), both of which are oncogenic types. The most prevalent species was nononcogenic α3. CONCLUSIONS HPV infection is common among US females, with the highest burden of infection found in young females 20-24 years of age. Monitoring trends in HPV type distribution will contribute to our understanding of the early impact of HPV vaccines.

Human Papillomavirus-Associated Cancers - United States, 2008-2012.

Human papillomavirus (HPV) is a known cause of cervical cancers, as well as some vulvar, vaginal, penile, oropharyngeal, anal, and rectal cancers (1,2). Although most HPV infections are asymptomatic and clear spontaneously, persistent infections with one of 13 oncogenic HPV types can progress to precancer or cancer. To assess the incidence of HPV-associated cancers, CDC analyzed 2008-2012 high-quality data from the CDCs National Program of Cancer Registries and the National Cancer Institutes Surveillance, Epidemiology, and End Results program. During 2008-2012, an average of 38,793 HPV-associated cancers were diagnosed annually, including 23,000 (59%) among females and 15,793 (41%) among males. By multiplying these counts by the percentages attributable to HPV (3), CDC estimated that approximately 30,700 new cancers were attributable to HPV, including 19,200 among females and 11,600 among males. Cervical precancers can be detected through screening, and treatment can prevent progression to cancer; HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites (3). Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10% (3). Among the oncogenic HPV types, HPV 16 is the most likely to both persist and to progress to cancer (3). The impact of these primary and secondary prevention interventions can be monitored using surveillance data from population-based cancer registries.