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This national cohort study examines National Immunization Survey–Teen to assess the association of adolescents’ ability to consent to human papillomavirus vaccination without parental involvement with vaccination rates.

This cross-sectional study compares uptake rates of cervical cancer screening and adherence among US women who were vaccinated for human papillomavirus vs those who were not vaccinated.

Importance Oropharynx cancer (OPC) incidence has increased for several decades in the US. It is unclear when and how this trend will be affected by current HPV vaccination trends. Objective To assess the association of HPV vaccination with future OPC incidence in the US. Design, setting, and participants This population-based age-period-cohort analysis obtained OPC incidence data from the Surveillance, Epidemiology, and End Results program from 69 562 patients 34 to 83 years of age diagnosed with OPC. The HPV vaccination data were obtained from the National Immunization Survey-Teen (60 124 participants) and National Health Interview Survey (16 904 participants). Data were collected from January 1, 1992, to December 31, 2017. Age-period-cohort forecasting models projected expected 2018 to 2045 OPC incidence under a counterfactual scenario of no HPV vaccination and current levels of HPV vaccination, stratifying by sex. Data analyses were completed by December 2020. Exposures Age- and sex-specific cumulative prevalence of HPV vaccination in 2016 to 2017 projected forward. Main outcomes and measures Projected OPC incidence and number of OPC cases expected to be prevented by HPV vaccination. Results Under current HPV vaccination rates, between 2018 and 2045, OPC incidence is projected to decrease in younger individuals (36-45 years of age: from 1.4 to 0.8 per 100 000 population; 46-55 years of age: from 8.7 to 7.2 per 100 000 population) but continue to increase among older individuals (70-83 years of age: from 16.8 to 29.0 per 100 000 population). The association of HPV vaccination with overall OPC incidence through 2045 will remain modest (no vaccination vs vaccination: 14.3 vs 13.8 per 100 000 population in 2045). By 2045 HPV vaccination is projected to reduce OPC incidence among individuals 36 to 45 years of age (men: 48.1%; women: 42.5%) and 46 to 55 years of age (men: 9.0%; women: 22.6%), but among those 56 years or older, rates are not meaningfully reduced. Between 2018 and 2045, a total of 6334 OPC cases will be prevented by HPV vaccination, of which 88.8% of such cases occur in younger age (≤55 years) groups. Conclusions and relevance According to the projections of this population-based age-period-cohort study, current HPV vaccination rates will have a limited association with overall OPC incidence through 2045 because older individuals who have not yet been vaccinated remain at high risk for OPC. However, reductions in OPC incidence should occur among young and middle-aged adults, the group at lowest risk of diagnosis. These findings forecast a continued shift in the landscape of OPC to an older population.

Vaccination against the human papillomavirus (HPV) is effective at preventing several squamous cell carcinomas, yet the population-level uptake of the vaccine remains low in the US. Several factors contribute to HPV vaccine hesitancy and refusal; of note, safety concerns rank consistently high as a reason for nonvaccination.1,2 The COVID-19 pandemic has brought to the forefront the fragility of public confidence in the safety of vaccines.3 Therefore, this study examines safety concerns or adverse effects of the HPV vaccine as the main reason for nonvaccination over an 11-year period.

Key Points Question Does public sentiment of human papillomavirus (HPV) vaccine safety align with spontaneous HPV vaccine adverse event reporting data? Findings This cross-sectional analysis of the 2015 to 2018 National Immunization Survey indicates a 79.9% increase in the proportion of parents who refused the HPV vaccine for their adolescents due to safety concerns. In contrast, estimates from the national vaccine safety surveillance system found that the HPV vaccine adverse event reporting rate per 100 000 doses distributed decreased from 44.7 in 2015 to 29.4 in 2018. Meaning These findings suggest an urgent need to combat safety concerns about the HPV vaccine in the US., This cross-sectional study investigates trends in human papillomavirus (HPV) vaccine adverse event reporting and trends in HPV vaccine safety concerns among caregivers of vaccine-eligible US adolescents from 2015 to 2018., Importance In the US, safety concern has been identified as a primary barrier to initiating the human papillomavirus (HPV) vaccine. It is unclear if the public’s sentiment concerning HPV vaccine safety aligns with postmarketing vaccine safety surveillance data. Objective To perform a parallel assessment of trends in HPV vaccine safety concerns and HPV vaccine adverse event (AE) reporting. Design, Setting, and Participants This study was a cross-sectional analysis of the National Immunization Survey (NIS) and Vaccine Adverse Event Reporting System (VAERS). Participants in the NIS were adolescents aged 13 to 17 years. AEs were reported to VAERS by patients, health care clinicians, or other sources. Statistical analysis was performed from October 2020 to May 2021. Main Outcomes and Measures Secular trends in HPV vaccine safety concerns and spontaneous AE reporting for HPV vaccination from 2015 to 2018. Results Caregivers of 39 364 unvaccinated adolescents with a mean (SD) age of 15.57 (0.08) years (26 996 White adolescents [62.9%], 22 707 male adolescents [56.1%], 11 392 privately insured [62.6%], and 32 674 above the poverty level [79.3%]) reported their reasons for not initiating the HPV vaccine series in the 2015-2018 NIS. Citing safety concerns as the primary reason for not initiating the HPV vaccine series increased from 13.0% (95% CI, 12.1%-14.0%) in 2015 to 23.4% (95% CI, 21.8%-25.0%) in 2018 (P for trend

Importance Missed opportunities for human papillomavirus (HPV) vaccination during pediatric health care visits are common. Objectives To evaluate the effect of online communication training for clinicians on missed opportunities for HPV vaccination rates overall and at well-child care (WCC) visits and visits for acute or chronic illness (hereafter referred to as acute or chronic visits) and on adolescent HPV vaccination rates. Design, Setting, and Participants From December 26, 2018, to July 30, 2019, a longitudinal cluster randomized clinical trial allocated practices to communication training vs standard of care in staggered 6-month periods. A total of 48 primary care pediatric practices in 19 states were recruited from the American Academy of Pediatrics Pediatric Research in Office Settings network. Participants were clinicians in intervention practices. Outcomes were evaluated for all 11- to 17-year-old adolescents attending 24 intervention practices (188 clinicians) and 24 control practices (177 clinicians). Analyses were as randomized and performed on an intent-to-treat basis, accounting for clustering by practice. Interventions Three sequential online educational modules were developed to help participating clinicians communicate with parents about the HPV vaccine. Weekly text messages were sent to participating clinicians to reinforce learning. Statisticians were blinded to group assignment. Main Outcomes and Measures Main outcomes were missed opportunities for HPV vaccination overall and for HPV vaccine initiation and subsequent doses at WCC and acute or chronic visits (visit-level outcome). Secondary outcomes were HPV vaccination rates (person-level outcome). Outcomes were compared during the intervention vs baseline. Results Altogether, 122 of 188 clinicians in intervention practices participated; of these, 120, 119, and 116 clinicians completed training modules 1, 2, and 3, respectively. During the intervention period, 29 206 adolescents (14 664 girls [50.2%]; mean [SD] age, 14.2 [2.0] years) made 15 888 WCC and 28 123 acute or chronic visits to intervention practices; 33 914 adolescents (17 069 girls [50.3%]; mean [SD] age, 14.2 [2.0] years) made 17 910 WCC and 35 281 acute or chronic visits to control practices. Intervention practices reduced missed opportunities overall by 2.4 percentage points (−2.4%; 95% CI, −3.5% to −1.2%) more than controls. Intervention practices reduced missed opportunities for vaccine initiation during WCC visits by 6.8 percentage points (−6.8%; 95% CI, −9.7% to −3.9%) more than controls. The intervention had no effect on missed opportunities for subsequent doses of the HPV vaccine or at acute or chronic visits. Adolescents in intervention practices had a 3.4-percentage point (95% CI, 0.6%-6.2%) greater improvement in HPV vaccine initiation compared with adolescents in control practices. Conclusions and Relevance This scalable, online communication training increased HPV vaccination, particularly HPV vaccine initiation at WCC visits. Results support dissemination of this intervention. Trial Registration ClinicalTrials.gov Identifier:NCT03599557

Key Points Question As human papillomavirus (HPV)–based cervical screening modalities change and HPV vaccination becomes more widespread, what are the likely outcomes for the interpretation of screening modalities? Findings In this decision analytical model with a simulated population of women aged 25 years and older, HPV-based screening modalities detected more abnormal cervical cells than traditional liquid-based cytology (LBC) approaches, but they did so at the cost of increased false positives. However, as HPV vaccination increased, HPV-based modalities resulted in fewer unnecessary colposcopies than LBC methods. Meaning These findings suggest that the ideal screening modality for a given population should account for HPV vaccination status to maximize the efficiency of screening., This decision analytical model estimates the likely outcomes of different screening modalities and models the effect of growing uptake of the human papillomavirus (HPV) vaccine on the interpretation of screening results., Importance Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. Objectives To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. Design, Setting, and Participants This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged ≥25 years), considering different levels of HPV vaccination. Main Outcomes and Measures The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. Results In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies). Conclusions and Relevance In this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.

This study uses data from the 2010-2018 National Health Interview Survey to characterize trends in human papillomavirus (HPV) vaccination rates, ages at vaccination, and numbers of doses received among young adults in the US between 2010 and 2018.

Importance Human papillomavirus (HPV) vaccination coverage is suboptimal in the US. The association between HPV vaccination requirements for school entry and HPV vaccination coverage remains to be studied. Objective To examine the association between HPV vaccination school-entry requirements and vaccination initiation in jurisdictions with such vaccination policies (ie, Virginia, the District of Columbia, and Rhode Island) compared with other regions of the US, as determined by the National Center for Chronic Disease Prevention and Health Promotion. Design, Setting, and Participants In a population-based, cross-sectional study, 2017 data from the National Immunization Survey–Teen database were used to determine HPV vaccination initiation. Data from 2008 to 2017 were then examined to assess the association between HPV vaccination school-entry policies and vaccination initiation. Data were obtained for adolescents aged 13 to 17 years in the US with health care professional–reported HPV vaccination histories (cross-sectional study, n = 4784; pre-post policy comparisons, n = 42 431). This study was conducted from May 1, 2019, to March 31, 2020. Exposures State-level HPV vaccination school-entry requirements from 2008 to 2017. Main Outcomes and Measures Health care professional–confirmed HPV vaccination initiation. Results The 2017 cross-sectional study included 4784 adolescents aged 13 to 17 years (2228 [46.6%] girls; 2556 [53.4%] boys; mean [SD] age, 15.0 [1.4] years; interquartile range, 14-16 years). Compared with nonpolicy jurisdictions within the same region, Rhode Island and the District of Columbia, which have HPV immunization school-entry requirements, had higher levels of HPV vaccination initiation (Rhode Island: adjusted odds ratio [aOR], 4.34; 95% CI, 2.16-10.00; District of Columbia: aOR, 2.35; 95% CI, 1.39-4.19). However, compared with regional nonpolicy states, Virginia’s HPV vaccination initiation did not differ significantly (aOR, 1.01; 95% CI, 0.72-1.42). The 2008-2017 pre-post policy comparisons involved 42 431 adolescents aged 13-17 years (22 362 [52.7%] girls; 20 069 [47.3%] boys; mean [SD] age, 15.0 [1.4] years; interquartile range, 14-16 years). Postpolicy levels of HPV vaccination initiation in girls was significantly higher in Rhode Island (aOR, 3.12; 95% CI, 1.92-5.07) than prepolicy values. Similar changes were noted for postpolicy HPV vaccination initiation in boys in the District of Columbia (aOR, 6.36; 95% CI, 4.27-9.46) and Rhode Island (aOR, 5.84; 95% CI, 3.92-8.69) compared with prepolicy measures. With respect to regional nonpolicy states during the same period, both girls and boys in Rhode Island and boys in the District of Columbia experienced larger increases in HPV vaccination initiation. For example, in Rhode Island, boys aged 16 to 17 years had 7.32 (95% CI, 3.56-15.06) times the change in pre-post policy HPV vaccination initiation, while girls aged 16 to 17 years had 1.28 (95% CI, 0.60-2.73) times the change. In the District of Columbia, boys had 6.36 (95% CI, 4.27-9.46) times the change in pre-post policy HPV vaccination initiation. Conclusions and Relevance The findings of this study suggest that HPV vaccination school-entry requirements are associated with increases in vaccination initiation. Expanding such policies may increase HPV vaccination in the US.

IMPORTANCE: Human papillomavirus (HPV) infection is found in about 40% of women who survive allogeneic hematopoietic stem cell transplant and can induce subsequent neoplasms. OBJECTIVE: To determine the safety and immunogenicity of the quadrivalent HPV vaccine (HPV-6, -11, -16, and -18) in clinically stable women post–allogeneic transplant compared with female healthy volunteers. INTERVENTIONS: Participants received the quadrivalent HPV vaccine in intramuscular injections on days 1 and 2 and then 6 months later. DESIGN, SETTING, AND PARTICIPANTS: This prospective, open-label phase-1 study was conducted in a government clinical research hospital and included clinically stable women posttransplant who were or were not receiving immunosuppressive therapy compared with healthy female volunteers age 18 to 50 years who were followed up or a year after first receiving quadrivalent HPV vaccination. The study was conducted from June 2, 2010, until July 19, 2016. After all of the results of the study assays were completed and available in early 2018, the analysis took place from February 2018 to May 2019. MAIN OUTCOMES AND MEASURES: Anti-HPV-6, -11, -16, and -18–specific antibody responses using L1 virus-like particle enzyme-linked immunosorbent assay were measured in serum before (day 1) and at months 7 and 12 postvaccination. Anti-HPV-16 and -18 neutralization titers were determined using a pseudovirion-based neutralization assay. RESULTS: Of 64 vaccinated women, 23 (35.9%) were receiving immunosuppressive therapy (median age, 34 years [range, 18-48 years]; median 1.2 years posttransplant), 21 (32.8%) were not receiving immunosuppression (median age, 32 years [range, 18-49 years]; median 2.5 years posttransplant), and 20 (31.3%) were healthy volunteers (median age, 32 years [range, 23-45 years]). After vaccine series completion, 18 of 23 patients receiving immunosuppression (78.3%), 20 of 21 not receiving immunosuppression (95.2%), and all 20 volunteers developed antibody responses to all quadrivalent HPV vaccine types (P = .04, comparing the 3 groups). Geometric mean antibody levels for each HPV type were higher at months 7 and 12 than at baseline in each group (all geometric mean ratios >1; P

This cross-sectional study examines trends in the diagnosis of anogenital warts over the course of 5 years in Connecticut, a state that achieved moderate uptake of human papillomavirus vaccine.

More than a decade after the introduction of the human papillomavirus (HPV) vaccine in the United States, only 51.1% of adolescents have completed the vaccine series, while a greater number (68.1%) received at least 1 dose.1 The suboptimal series completion rate in the United States is partly attributable to the barriers, including unawareness of or forgetting the need for additional doses, lack of insurance coverage or health care professional recommendations, and less frequent contact with the medical system.2,3 To simplify the recommendations, trials are evaluating the efficacy of a single-dose regimen.4 In this study, we investigated HPV infection prevalence among women by number of vaccine doses received.

Physicians must educate patients and parents about the risks and benefits of the HPV vaccine to increase rates of vaccination and decrease racial and sex disparities in access to the vaccine.

Importance Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, and oral HPV infection is associated with increased risk of oropharyngeal cancer. Objective To describe the risk factors for oral HPV in sexually active female adolescents receiving the quadrivalent vaccine. Design, Setting, and Participants Longitudinal cohort study involving repeated collection of oral rinse specimens from sexually active female adolescents conducted between October 19, 2007, and March 9, 2017, at a large adolescent health center in New York, New York, that provides free health care, including HPV vaccination. Exposures Human papillomavirus vaccination and self-reported history of sexual behavior. Main Outcomes and Measures Prevalence of HPV in the oral cavity. Results Among the 1259 participants who were included in this study, median age at entry into the study was 18 (range, 13-21) years; 638 (50.7%) were of African American descent, 569 (45.2%) were of Hispanic descent, 43 (3.4%) reported another race/ethnicity, and race/ethnicity was unspecified for 9 (0.7%). The median (mode) age at first sexual activity was 14.8 (14) years, and 1161 (92.2%) reported having had oral sex. Human papillomavirus DNA was detected in baseline oral rinse samples of 78 of the 1259 participants (6.2%; 95% CI, 4.9%-7.6%). There was a significant decrease in oral HPV detection with time (in years) since first engaging in sexual activities, independent of age and concurrent detection of cervical HPV; comparing 4 or more years with 1 year or less, the odds ratio was 0.45 (95% CI, 0.21-0.96). Detection of vaccine types (HPV-6, HPV-11, HPV-16, and HPV-18) was significantly lower among participants who had received at least 1 dose of the quadrivalent HPV vaccine at the time of enrollment compared with those who were unvaccinated (odds ratio, 0.20; 95% CI, 0.04-0.998). Conclusions and Relevance This study’s findings suggest that detection of HPV in the oral cavity is not uncommon in sexually active female adolescents. In addition, HPV vaccination is associated with a significant decrease in detection of HPV vaccine types in the oral cavity.

Importance Squamous cell carcinoma (SCC) is the second most common form of skin cancer, and its incidence is increasing. When surgical management is not an option, finding a safe and efficacious treatment is a challenge. Mounting evidence suggests that the human papillomavirus (HPV) is involved in the pathogenesis of some SCCs. Objective To assess whether the 9-valent HPV vaccine could be an effective treatment strategy for cutaneous SCC. Design, Setting, and Participants A woman in her 90s with multiple, inoperable cutaneous basaloid SCCs was successfully treated at a university-based outpatient dermatology clinic with a combination of systemic and intratumoral delivery of the 9-valent HPV vaccine from March 17, 2016, through February 27, 2017, and then followed up through May 21, 2018. Main Outcomes and Measures Reduction in tumor size and number after a combination of systemic and intratumoral administration of the HPV vaccine. Results All tumors resolved 11 months after the first intratumoral injection of the vaccine. The patient remained free of tumors at the end of follow-up. Conclusions and Relevance This is the first report, to our knowledge, of complete regression of a cutaneous malignant tumor after combined systemic and direct intratumoral injection of the 9-valent HPV vaccine. This report suggests that the HPV vaccine may have therapeutic utility for SCCs in patients who are poor surgical candidates, have multiple lesions, or defer surgery.

The 2017 Lasker-DeBakey Clinical Medical Research Award has been presented to Douglas Lowy and John Schiller for development of the virus-like particle technology that was used to create the human papillomavirus vaccine to prevent cervical cancer and other diseases.

Importance A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. Objective To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. Design, Setting, and Participants The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Main Outcome Measures Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). Results From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], −9.0; 95% CI, −12.0 to −5.8; P P = .03), and from 240.2 to 0 for CIN3 (APC, −41.3; 95% CI, −65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, −6.3; 95% CI, −10.9 to −1.4; P = .02). Conclusions and Relevance Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

Importance Keratinocyte carcinomas (KCs), consisting of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), are the most common human malignant neoplasms. Several risk factors have been implicated in KC development. For some SCCs, particularly those in immunocompromised patients, human papillomavirus (HPV) may be an important factor. Objective To determine whether quadrivalent HPV vaccination would affect the development of KCs in immunocompetent patients with a history of multiple KCs. Design, Setting, and Participants Two patients with a history of multiple KCs—a man in his 70s (patient 1) and a woman in her 80s (patient 2)—were treated in a private dermatology practice. Each patient received 3 doses of the quadrivalent HPV vaccine at 0, 2, and 6 months in 2013, and both patients underwent full-body skin examinations at least every 3 months. Biopsy-proven skin cancers were recorded for 16 months (for patient 1) or 13 months (for patient 2) after the first dose of vaccine and then compared with the number of biopsy-proven skin cancers recorded over a similar period before the first dose of vaccine. The period of observation was from October 18, 2011, to June 21, 2014. Main Outcomes and Measures The numbers of new SCCs and BCCs after the first dose of the quadrivalent HPV vaccine. Results Patient 1 had a mean of 12 new SCCs and 2.25 new BCCs per year before vaccination. After vaccination, he developed 4.44 SCCs and 0 BCCs per year, a 62.5% reduction in SCCs and a 100% reduction in BCCs. Patient 2 had a mean of 5.5 new SCCs and 0.92 new BCCs per year before vaccination. After vaccination, she developed 1.84 SCCs and 0 BCCs per year, a 66.5% reduction in SCCs and a 100% reduction in BCCs. The quadrivalent HPV vaccine was well tolerated by both patients and had no adverse effects. Conclusions and Relevance A reduction of SCCs and BCCs was observed in 2 patients after administration of the quadrivalent HPV vaccine. These findings highlight the possibility that cutaneous SCC development, and perhaps BCC development, may be driven in part by HPV in immunocompetent patients. Human papillomavirus vaccination may represent an efficacious, cost-effective, readily available, and well-tolerated strategy for preventing KCs.

Importance The quadrivalent human papillomavirus (HPV) vaccine was licensed for use in 9- through 26-year-old females in 2006. Postlicensure studies in Australia, Denmark, and Canada have demonstrated vaccine effectiveness against abnormal cervical cytology results. However, there are limited data describing postlicensure effectiveness in the United States, particularly among minority females at higher risk for HPV infection and cervical cancer. Objective To examine the effect of HPV vaccination on abnormal cervical cytology results among minority females. Design, Setting, and Participants Retrospective cohort study conducted between January 2007 and January 2014 at 16 academically affiliated community clinics serving a low-income minority population. Included in this study was a population-based sample of 16 266 females aged 11 through 20 years as of January 1, 2007, who received care at a participating clinic on or after that date. Exposure Human papillomavirus vaccination, stratified by the number of doses. Main Outcomes and Measures Cervical cytology abnormality following either HPV vaccination or, if unvaccinated, the first missed opportunity for HPV vaccination after January 1, 2007. Abnormalities were defined as atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions. Results There were 4127 female patients who initiated quadrivalent HPV vaccination or had their first missed HPV vaccination opportunity from 11 through 20 years of age and underwent subsequent cervical cytology screening. The patients were primarily Spanish speaking (n = 2297; 58.3%) and publicly insured (n = 3801; 92.1%). The detection rate for an abnormal cervical cytology result during the observation period was lower among vaccinated (≥1 dose) (79.1 per 1000 person-years) vs unvaccinated (125.7 per 1000 person-years) females. The risk for an abnormal cervical cytology result was lower among vaccinated vs unvaccinated females (hazard ratio [HR], 0.64; 95% CI, 0.57-0.73), particularly if the 3-dose series was completed (HR, 0.48; 95% CI, 0.41-0.56) or if the vaccine was administered from 11 through 14 years of age (≥1 dose: HR, 0.36; 95% CI, 0.16-0.79; 3 doses: HR, 0.27; 95% CI, 0.12-0.63). This protective effect remained after adjusting for demographics, clinic type, abnormal baseline cervical cytology result, and baseline Chlamydia screening (as proxy for sexual experience). Conclusions and Relevance This study demonstrated the HPV vaccine is effective in a real-world setting of high-risk patients with variable HPV vaccination patterns.

Rodney Willoughby, MD, a pediatric infectious disease specialist at the Medical College of Wisconsin, can’t help thinking about the future—a future in which thousands of men and women developprecancerousorcancerous lesionsthat could have been prevented had they been vaccinated against the human papillomavirus (HPV) as 11or 12-year-olds. “The family practitioners and pediatricians do a really bad job in promoting HPV vaccination for a variety of reasons,” said Willoughby, amemberof theAdvisoryCommittee on Immunization Practices’ (ACIP) working group on the HPV vaccine and the American Academy of Pediatrics’ Committee on Infectious Diseases. “We recognize that we are falling down on the job. This is actually a real emergency.” Research has shown thatmost parents would immunize their children if their pediatrician or family practitioner recommendedtheHPVvaccineaspartof thestandard package of vaccines for adolescents (Holman DM et al. JAMA Pediatr. 2014; 168[1]:76-82, and Rickert VI et al. Vaccine. 2015;33[5]:642-647). But studies alsohave found that parents, like physicians, sometimes delay immunization because they think their child is years away from becoming sexually active and contracting HPV. In addition, theHPVvaccine requires3 trips to the physician’s office, which might prove daunting to busy families. The urgency for vaccination is underscoredby the fact thatHPV is themost common sexually transmitted infection, and most sexually active men and women become infected at least once during their life (http://1.usa.gov/1NZJvwU).Moreover, persistent infectionwith certain strains causes virtually all cervical cancers aswell as about two-thirds of vulvar and penile cancers, three-fourths of vaginal and oropharyngeal cancers, and about 9 in 10 anal cancers (http://1.usa.gov/1CjY7nN). Human papillomavirus vaccines can’t prevent infectionafter the fact,which iswhy theACIPrecommends immunizationforpreteens before they become sexually active. The ACIP has recommended routine vaccinationofgirls aged 11or 12years since2006, when Gardasil, the first approved HPV vaccine, became available (http://1.usa.gov /1DoEGKj). The committee issued the same recommendation for boys in 2011 (http://1 .usa.gov/1G97qVc). Gardasil, Merck’s quadrivalent vaccine approved for males and females, protects against 2 HPV types (16 and 18) that cause 70% of cervical cancers as well as 2 other HPV types (6 and 11) responsible for 90% of genital warts cases. Cervarix, GlaxoSmithKl ine’s bivalent vaccine approved only for girls, protects against the same 2 cancer-causing types of HPV (http: //bit.ly/1wPTsYd). In December, the Food and Drug Administration approved the 9-valent HPV vaccine (9vHPV), Gardasil 9, which protects against HPV types in the original quadrivalent vaccine and an additional 5 HPV types that cause cervical cancers (http://1.usa.gov/1LiJp4E). ACIP recently updated its HPV vaccine recommendations to include 9vHPV as one of the three recommended vaccines that can be used for routine immunization (Petrosky E et al. MMWR Morb Mortal Wkly Rep. 2015; 64[11]:300-304). Humanpapillomavirus types 16 and 18, associatedwith cervical cancer, are also associatedwithpenileandoropharyngeal cancer. Although the HPV vaccines are presumed toprotect against those2 cancers as well as cervical cancer, clinical trialshavenot yet been conducted to demonstrate efficacy against these cancers (http://1.usa.gov /18tjZiY). Such studies would be prohibitively long and expensive, Willoughby said, because researchers have nothing comparable to thePap smear to detect precancerous penile or oropharyngeal lesions. Despite the preventive benefits and documented efficacy in protecting against cervical cancer, HPV vaccination rates remain far below 2 other recommended preteen vaccines—the one for Tdap (against tetanus, diphtheria, and pertussis) and the meningococcal conjugate vaccine (ElamEvansLDetal.MMWRMorbMortalWklyRep. 2014;63[29]:625-633). In 2013, 86%ofUS teens aged 13 to 17 years had received Tdap and77.8%had received themeningococcal vaccine. But only 57.3% of girls and 34.6% of boys had received at least 1 of the 3 recommendeddoses ofHPVvaccine, and only 37.6%of girls had receivedall 3 doses (http: //kff.org/womens-health-policy/fact-sheet /the-hpv-vaccine-access-and-use-in/). These vaccination rates fall far short of the Healthy People 2020 initiative’s target goal to have 80% of 13to 15-year-old girls and boys fully immunized with all 3 HPV doses (http://1.usa.gov/1MFXTH7). Medical News&Perspectives .....p1502

Comparedwithotherroutinelyrecommendedadolescentvaccines (eg, diphtheria and tetanus toxoids andacellular pertussis [Tdap] vaccine and quadrivalent meningococcal conjugate [MCV4] vaccine), human papillomavirus (HPV) vaccine uptake has been lower, with only 57% of adolescent females and 35% of adolescent males initiating the 3-dose HPVvaccine series.1Often, the reasons cited for these lowHPV vaccination rates pertain to the vaccine’s role in preventing a sexually transmitted infection (STI). Parents commonly indicate that they have not had their children vaccinated against HPV because the vaccine is not needed or because their child isnot sexually active,2 andevensomephysicians expresshesitancy toward strongly recommending the HPV vaccine. In a recently published series of qualitative interviews,3 physiciansexpressedconcernsaboutdiscussing sexual activitywith 11-and12-year-oldsand indicatedpreferences fordeferringvaccination to later ages.However, just aswedonotwait untilwe havebeen in the sun for 2hours to apply sunscreen,we should not wait until after an individual is sexually active to attempt to prevent HPV infection. Thehesitancyon thepart ofparents andphysicians tovaccinateordiscussvaccinationmaybeattributable toworries that HPV vaccinationwill be seen as a tacit approval for sexual activity. Concerns about increased sexual activity and risk disinhibitionhave beendiscussed since before the initial recommendation forHPVvaccination. In this issueof JAMA Internal Medicine, Jenaet al4 add to the literaturebypresenting anovel analysis that indicates no evidence for increased sexual activity after HPV vaccination. Jena et al evaluated STI-related insurance claims formore than200 000adolescent (aged12-18years) females insuredfrom January1,2005, throughDecember31,2010, intheUnitedStates. The researchersmatchedvaccinatedandunvaccinatedadolescents by age andkeyedonan indexquarter (quarter of theyear that included vaccination date for the vaccinated adolescents) for assessment of risk of STI claims. If analyseswere limited to onlydirectmeasuresofpostvaccinationSTI-relatedclaims, results couldbebiasedby longitudinal increases inSTI rateswith increasing age and potential selection bias related to prevaccinationdifferences inSTI riskamongHPVvaccine recipients.To accountfor thisbias, theresearcherscomputedoddsratios (ORs) for the association between the vaccine and sexual activity for 1-year periods before and after the index quarter and conductedadifference-in-differenceanalysisby taking the ratioof thepostvaccinationORrelative to theprevaccinationOR.Thus, the difference-in-difference OR of 1.05 (95% CI, 0.80-1.38) reported by Jena et al indicates that there was no increased risk ofSTI claimsamongHPVvaccinees relative tononvaccineesafter adjustment for preindex quarter STI risk.4 This patternwas consistent after stratification by age and restriction to adolescent females with insurance claims for contraceptives in their vaccine index quarter. These subanalyses indicate that even amongthosewhomayhavealreadybeensexuallyactive, sexual activity levels, as measured by incidence of STIs, did not increase after HPV vaccination. These findings should not come as a surprise to researchers in the field of HPV vaccinology and should serve as continuedreassurancethatHPVvaccinationdoesnot leadtosexual disinhibition. However, this reassurance leaves us with the question, “How can we use these findings to address concerns of anxious parents of adolescents?” Concerns about HPV vaccine are not always directly expressed in termsofpotential for increasing sexual activity;parentsoftenexpress concernsabout the recommendedageof the vaccine.According to the2013National ImmunizationSurvey– Teen, among parents of 13through 17-year-olds included in the survey who did not intend to have their children receive HPVvaccine in the next year, 15% indicated they believed the vaccine was not needed or not necessary, and 11% indicated their child was not sexually active.2 These concerns overlook the 3major reasonswhyHPV vaccine is recommended for 11and 12-year-olds. First, the antibody response in younger adolescents (9-15 yearsofage) isgreater forallHPVtypes in thequadrivalentHPV vaccine than it is in older adolescents and young adults (16-26 years of age).5 Second, estimates from the 2006-2010National Survey of Family Growth indicate that, by 15 through 17 years of age, 27% of adolescents in the United States have ever had sexual intercourse; by 18 through 19 years of age, this proportion increases to 63%.6 Third, with the Tdap and MCV4 vaccines also recommended for 11and 12-year-olds, health care professionalscanleveragethewell-childvisit for11-and12-yearolds recommended by the American Academy of Pediatrics to administertheTdapandMCV4vaccinesandinitiatetheHPVvaccine series, reducingmissed opportunities for vaccination.2 It is not just parentswhoneed this information, however. Physicianshave indicated reluctance to recommendHPVvaccinewith the sameemphasisused for theTdapandMCV4vaccines, citing concerns about discussing sexual activity or lack ofperceivedsusceptibilityofHPV infectionorHPV-relateddiseasesamong11and12-year-olds.3Weoften thinkof theHealth Belief Model constructs (perceived susceptibility and perceived severity) as they relate to an individual’s choice to elect apreventivevaccination.However, these constructs alsoneed to be considered in terms of physicians’ perceptions of their patients’ riskofdisease.Fromqualitative interviewswithphysicians, Perkins et al3 highlighted physician concerns, including, “I don’t get as scaredof cervical cancer just because... the Related article page 617 Research Original Investigation STIs After HPV Vaccination

Importance A new diagnosis of adult-onset recurrent respiratory papillomatosis (AO-RRP) prompts many questions related to disease acquisition, course, and transmission. Recent attention to the human papillomavirus (HPV), along with emerging data on AO-RRP, provides a foundation for patient counseling. Objective To provide a framework for these discussions, including an overview of the current literature on HPV-mediated disease across organs. Evidence Review The peer-reviewed literature was culled to provide a comprehensive review encompassing AO-RRP and anogenital papilloma, as well as general HPV virology and pathophysiology. PubMed and Google Scholar databases were searched from 1975 to July 2014. Findings Most HPV infections in healthy adults are cleared within 2 years without clinical significance. Adult-onset RRP is a rare manifestation of HPV and may be homologous to anogenital HPV, which is highly transmissible between sexual partners. Horizontal transmission of AO-RRP has not been characterized. Our laboratory, however, recently found that nearly 100% of patients with AO-RRP had concurrent oral cavity HPV infection. Historically, an increased number of oral sex partners was thought to be associated with AO-RRP, but recent data from our group did not corroborate this finding. Recent data also question the dogma that smoking and laryngopharyngeal reflux play a role in recidivistic disease. Management of AO-RRP is often symptom based and includes lesion excision or ablation with adjuvant therapies including cidofovir for refractory cases. Conclusions and Relevance Recurrent respiratory papillomatosis may be related to a new or latent HPV infection, potentially obtained at birth, and the mechanism(s) underlying the progression from HPV infection to RRP remains unknown. Recommendations with regard to sexual practices in patients with AO-RRP cannot be made at this time. Unlike human immunodeficiency virus, patients with AO-RRP are not obligated to discuss infection status with partners. Despite the nebulous nature of the disease, clinicians should be a resource to discuss the current state of the literature with both the patient and partner.

IMPORTANCE Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine. OBJECTIVE To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS An open cohort of all females aged 10 to 24 years living in Sweden (n = 1 045 165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers. MAIN OUTCOMES AND MEASURES Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting. RESULTS A total of 20 383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100 000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100 000 person-years. CONCLUSIONS AND RELEVANCE Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.

Importance Understanding head and neck surgeons’ current knowledge, practices, and opinions regarding human papillomavirus (HPV) education and prevention will enable efforts to assist surgeons in this important endeavor. Objective To assess knowledge, attitudes, and beliefs of head and neck surgeons regarding HPV education and vaccination. Design, Setting, and Participants Online survey of members of the American Head and Neck Society (AHNS) in late 2011 and early 2012. Main Outcomes and Measures Knowledge, attitudes, and current practices regarding HPV education and vaccination. Results All 1081 members of the AHNS were approached via e-mail, and 297 members completed the survey, for an overall response rate of 27.5%. Most respondents were male (86.2%) fellowship-trained head and neck surgeons (80.4%), and most practice in an academic setting (77.1%) in the United States (78.1%). More than 90% of respondents discuss risk factors for head and neck cancer and HPV as a specific risk factor with their patients. However, only 49.1% discuss the importance of vaccinating preadolescents for HPV, most commonly citing that they do not do so because their patients are adults (38.7%). Of those respondents with daughters, 68.9% reported that their daughters had received or they intend their daughters to receive the HPV vaccine. Of those respondents with sons, only 55.8% reported that their sons had been vaccinated or they intend for them to be. Respondents reported divergent attitudes toward HPV vaccination safety and efficacy. However, respondents were overwhelmingly supportive of possible future ANHS activities to educate clinicians, increase public awareness, educate patients, and advocate for health policy related to HPV. Conclusions and Relevance Head and neck surgeons are knowledgeable about HPV and show generally positive attitudes and beliefs about HPV education and vaccination. They endorse AHNS actions to improve public and patient education, as well as health policy on HPV. These findings support AHNS developing a strategic plan and actions to improve knowledge and reduce HPV infection among the American public.

Cervical cancer is the second most common cancer among women globally, according to age-standardized incidence rates.1 Approximately 530 000 women are diagnosed with cervical cancer and 275 000 die of the disease every year; 88% of deaths occur in developing regions of the world.1 Human papillomavirus (HPV) infection is a well-established cause of cervical cancer as well as other anogenital and oropharyngeal cancers; therefore, prophylactic HPV vaccines have the potential to substantially reduce the incidence of cervical cancer and other HPV-associated diseases.2 Three-dose schedules of the bivalent vaccine (HPV-16 and -18) and the quadrivalent vaccine (HPV-6, -11, -16, and -18) have been shown to be highly efficacious in preventing persistent infection with HPV-16 and -18, which cause approximately 70% of cervical cancers, as well as precancerous lesions associated with these types.3- 5 The quadrivalent vaccine has also been shown to prevent anogenital warts associated with HPV-6 and -11.3,5

Objective To assess the safety of the quadrivalent human papillomavirus vaccine (HPV4) in females following routine administration. Design In a cohort of vaccinated females, we compared the risk of emergency department visits and hospitalizations during the interval soon after vaccination with risk during a comparison interval more remote from vaccination. Setting Kaiser Permanente in California. Participants All females who received the HPV4 vaccine. Main Exposure One or more doses of HPV4 between August 2006 and March 2008. Main Outcome Measures Outcomes were emergency department visits and hospitalizations, grouped into predefined diagnostic categories. Within diagnostic groups, we used odds ratios (ORs) to estimate whether each subject had any outcome in postvaccination risk intervals (days 1-60, days 1-14, and day 0), compared with a control interval distant in time from vaccination. Results One hundred eighty-nine thousand six hundred twenty-nine females received at least 1 dose and 44 001 received 3 HPV4 doses. Fifty categories had significantly elevated ORs during at least 1 risk interval. Medical record review revealed that most diagnoses were present before vaccination or diagnostic workups were initiated at the vaccine visit. Only skin infections during days 1 to 14 (OR, 1.8; 95% CI, 1.3-2.4) and syncope on day of vaccination (OR, 6.0; 95% CI, 3.9-9.2) were noted by an independent Safety Review Committee as likely associations with HPV4. Conclusions The quadrivalent human papillomavirus vaccine was associated with same-day syncope and skin infections in the 2 weeks after vaccination. This study did not detect evidence of new safety concerns among females 9 to 26 years of age secondary to vaccination with HPV4.

HEN DO PHYSICIANS KNOW ENOUGH ABOUT THE beneficial effects of a new medical interventiontostartrecommendingorusingit?When istheavailableinformationaboutharmfuladverse effects sufficient to conclude that the risks outweigh the potential benefits? If in doubt, should physicians err on the side of caution or on the side of hope? These questions are at the core of all medical decision making. It is a complicated process because medical knowledge is typically incomplete and ambiguous. It is especially complex to make decisions about whether to use drugs that may prevent disease in the future, particularly when these drugs are given to otherwise healthy individuals. Vaccines are examples of such drugs, and the human papillomavirus (HPV) vaccine is a case in point. zur Hausen, winner of the Nobel Prize in Physiology or Medicine in 2008, discovered that oncogenic HPV causes cervical cancer. 1-4 His discovery led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis, and eventuallytothedevelopmentofprophylacticvaccinesagainstHPV infection.

The new vaccine against 4 types of human papillomavirus (HPV), Gardasil, like other immunizations appears to be a cost-effective intervention with the potential to enhance both adolescent health and the quality of their adult lives. However, the messages and the methods by which the vaccine was marketed present important challenges to physician practice and medical professionalism. By making the vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to adolescents was maximized, and the subpopulations most at risk practically ignored. The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology. The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits. As important and appropriate as it is for PMAs to advocate for vaccination as a public good, their recommendations must be consistent with appropriate and cost-effective use.

Objectives (1) To synthesize sociocultural results from diverse populations related to vaccine decision-making, understanding of cervical cancer and its etiology, experience with previous vaccinations, human papillomavirus (HPV) vaccine concerns, and information needed to foster acceptance; (2) to contextualize findings in light of recent studies; and (3) to discuss implications for communication strategies to facilitate vaccine acceptance. Design Descriptive qualitative synthesis of sociocultural studies in 4 countries using iterative theme-based analyses. Setting Four developing countries: India, Peru, Uganda, and Vietnam. Participants Criterion-based sample of 252 focus-group discussions and 470 in-depth interviews with children, parents, teachers/administrators, health workers/managers, and community/religious leaders. A knowledge, attitudes, and practices survey was administered to 879 children and 875 parents in Vietnam. Results We found that vaccine decision-making was primarily done by parents, with children having some role. Understanding of cervical cancer and HPV was limited; however, the gravity of cancer and some symptoms of cervical cancer were recognized. Vaccination and government-sponsored immunization programs were generally supported by respondents. Sentiments toward cervical cancer vaccines were positive, but concerns about quality of delivery, safety, adverse effects, and the effect on fertility were raised. Communities requested comprehensive awareness-raising and health education to address these concerns. Conclusion Sociocultural studies help elucidate the complexities of introducing a new vaccine from the perspective of children, parents, and communities. Strategies for introducing the HPV vaccine should address community concerns through effective communication, appropriate delivery, and targeted advocacy to make the program locally relevant.

ContextViruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy.ObjectiveTo determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV.Design and SettingPhase 3, masked, community-based randomized trial conducted in 2 provinces of Costa Rica.ParticipantsA total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005. Participants were positive for HPV DNA at enrollment, had at least 6 months of follow-up, and had follow-up HPV DNA results.InterventionParticipants were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n = 1088) or a control hepatitis A vaccine (n = 1101) over 6 months.Main Outcome MeasuresPresence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination. We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit (after 2 doses) and 12-month visit (after 3 doses) in the 2 study groups.ResultsThere was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance, 2.5%; 95% confidence interval, −9.8% to 13.5%). Human papillomavirus 16/18 clearance rates at 12 months were 48.8% (86/177) in the HPV vaccine group and 49.8% (110/220) in the control group (vaccine efficacy for viral clearance, −2.0%; 95% confidence interval, −24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories, among women receiving all vaccine doses, among women with single infections, or among women stratified by the following entry variables: HPV-16/18 serology, cytologic results, HPV DNA viral load, time since sexual debut, Chlamydia trachomatis or Neisseria gonorrhoeae infection, hormonal contraceptive use, or smoking.ConclusionIn women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections.Trial Registrationclinicaltrials.gov Identifier: NCT00128661