Data were obtained from STD clinics participating in the Centers for Disease Control and Prevention’s STD Surveillance Network (SSuN) from January 2010 to December 2016 [27]. Data from 27 STD clinics in the following jurisdictions were included: Baltimore (2 clinics), Los Angeles (12), New York City (9, 2010–2014; 8, 2015–2016), Philadelphia (2), San Francisco (1), and Seattle (1). All jurisdictions submitted data through the entire study period. Analyses were restricted to visit types in which a patient was seen by a healthcare provider (ie, clinician visits); express/follow-up visits were excluded. Within each calendar year, patient visits were deduplicated so that unique patients per year were the unit of analysis. Demographic, behavioral, and clinical information was abstracted from electronic medical records and collated across patient visits per year. Human immunodeficiency virus (HIV) status was assessed through laboratory testing or, if known to be living with diagnosed HIV, self-reporting. Sexual behavior was determined by patient self-report of male and/or female sex partners or by self-reported sexual orientation (eg, “gay” or “straight”). Men who identified as gay or bisexual or who reported having sex with a man at any of their visits for the year were classified as MSM. Men who identified as heterosexual only or reported only female sex partners at any time during the year were classified as MSW. Sex partnerships among women were not considered, as only 2% of women reported having sex with women only. Six percent of the male population for whom the sex of sex partners was unknown were excluded from the trend analyses, as were patients who reported being transgender (<1%).

Approximately 650 000 patients had at least one clinician visit in a participating SSuN STD clinic from 1 January 2010 through 31 December 2016. The number of patients attending the clinics declined over the study period, from 108 524 patients in 2010 to 74 690 patients in 2016 (Table 1). The median age was 26 years for women (mean age [±SD], 28.9 ± 10.4 years), 29 years for MSW (mean age [±SD], 32.5 ± 11.3 years), and 31 years for MSM (mean age [±SD], 33.6 ± 10.7 years). The mean age (±SD) of all patients increased slightly over time, from 30.5 ± 11.0 years in 2010 to 33.0 ± 11.5 years in 2016. Approximately half of the population was non-Hispanic black; 21% of patients was Hispanic, and 20% was non-Hispanic white. Sixty-three percent of the population was male, and 29% of male patients were identified as MSM. The proportion of men who were MSM increased from 12.9% in 2010 to 23.4% in 2016. Approximately 4% of the population was known to be living with diagnosed HIV infection, although the proportion increased from 3.2% in 2010 to 5.2% in 2016; among MSM only, the proportion ranged from 18.0% to 19.2% but did not significantly increase over the study period. The proportion of patients known to be living with diagnosed HIV infection was higher among MSM (18.7%) than among MSW (0.9%) or women (0.7%). During 2015–2016, compared with the preceding years, there were increases in the proportion of patients for whom the following characteristics were unknown: age (from 0% to approximately 5%), sex (from <1% to approximately 5%), race/ethnicity (from approximately 3% to approximately 8%), and sex of sex partners (from approximately 2% to approximately 8%).

Substantial diversity in patient demographic characteristics and AGW prevalence existed across jurisdictions (data not shown). For example, across the study period, 31% of the patient population in Los Angeles was Hispanic, compared with 4% in San Francisco. Thirty-nine percent of the San Francisco patient population was MSM, compared with 5% in Baltimore. Eight percent of the San Francisco patient population was known to be living with diagnosed HIV infection, compared with 2% in Los Angeles. The jurisdiction with the highest prevalence of AGW during the study period was Seattle, at 5.5%, and the lowest was Baltimore, at 2.8%.

The overall prevalence of AGW, adjusted for jurisdiction, was highest in MSW (6.3%; 95% CI, 5.3%–7.4%), followed by MSM (4.6%; 95% CI, 4.2%–5.1%), and women (1.8%; 95% CI, 1.5%–2.1%). The overall unadjusted prevalence of AGW was 5.9% in MSW, 4.6% in MSM, and 1.6% in women.

Using STD clinic data, we report the first temporal trends in the prevalence of AGW in the United States, by patient sex and the sex of male patients’ sex partners. We document declines in the AGW prevalence across all populations, with statistically significant declines among women aged ≤39 years, among MSW aged ≤39 years, and among MSM of all ages. These declines suggest that HPV morbidity is decreasing among patients attending SSuN STD clinics. The drivers of these decreases are unclear. It is likely that some of the observed decreases may be related to expanded HPV vaccination coverage, but it is also possible that observed declines may have been influenced by changes in the patient population accessing care in STD clinics and/or by variations in AGW testing and diagnoses by STD clinic providers.

HPV vaccination may explain some of the observed declines, particularly among populations for which HPV vaccination is recommended. For example, the observed steady declines in women aged <30 years are consistent with what would be expected following the initiation of routine HPV vaccination; all women in this group would have been age eligible for HPV vaccination before or during the study period. Additionally, there were significant declines in the AGW prevalence in both MSM and MSW aged <40 years. The ACIP has recommended catch-up HPV vaccination for men through age 21 years since 2011; all male individuals aged <20 years and most aged 20–24 years would have been age eligible for vaccination during part of the study period. The prevalence among MSW aged 20–29 years remained stable from 2010 to 2012 but decreased significantly from 2012 to 2016. This inflection in trend in 2012 coincides with the ACIP’s October 2011 recommendation to vaccinate men. Declines in the AGW prevalence among MSW may also be partially attributed to herd protection from female vaccination, as female cervicovaginal HPV prevalence and female AGW morbidity in younger age groups has continuously decreased since the ACIP recommended female vaccination in 2006 [21, 22, 29]. Since 2011, the ACIP has recommended catch-up HPV vaccination for MSM through age 26 years. Similar to MSW, an inflection in trend was observed in 2012 for MSM aged 20–24 years. However, unlike MSW or women, statistically significant declines in AGW diagnoses among MSM >39 years were observed. Although older MSM are less likely to be HPV naive and may not directly benefit from vaccination, observed decreases may be partially due to herd protection via sex partnerships with younger men, which may be more common among MSM as compared to MSW or women [30].

The observed declines in populations that were not age eligible argue against vaccination being the primary catalyst for our observed findings and may reflect changes in the patient population attending these clinics. During the study period, the overall number of patients attending SSuN STD clinics decreased by approximately 30%, which would affect the absolute number of AGW diagnoses over time. We accounted for the decreasing population size by estimating AGW morbidity as a proportion of all patients; however, we were unable to account for possible changes in the attributes of patients attending STD clinics. If, over time, more persons with AGW chose to seek care in non-STD clinics, including private facilities and community health centers, we would observe a decline in clinic prevalence independent of changes in population prevalence. Changes in where people seek care for AGW may reflect changes in the healthcare system (eg, increasing insurance coverage may lead to more use of private facilities). Additionally, fiscal cuts to STD clinics may have resulted in changes in clinic operating hours and staff shortages, leading to a prioritization of patients with acute STIs, such as syphilis or symptomatic urethritis. Finally, because we estimated AGW morbidity as a proportion to account for changing clinic population size, the observed prevalence is affected by the incidence of other STIs in the general population. For example, if the syphilis incidence increases, more patients with syphilis would access care, and the observed clinic prevalence of AGW would decrease independent of the population prevalence.

Another possible explanation for the observed declines may be related to changes in clinical practice. The clinical criteria for identifying or diagnosing AGW did not change throughout the study period. However, there is no laboratory test for AGW, and HPV testing is not routine in STD clinics, so AGW are generally diagnosed by physical examination. It is possible that the proportion of AGW cases that were present but not detected or that were misdiagnosed increased over time owing to a decrease in physical examinations. If clinics increased self-collection of specimens for STI testing (eg, self-collected vaginal swabs for chlamydia testing), fewer patients may have had direct visual inspection of their genitals, resulting in fewer diagnoses of AGW independent of changes in population prevalence. This may be especially relevant for observed trends in female patients, as male genitalia may be easier to inspect visually as compared to female genitalia, which requires a pelvic examination. Because documentation of whether a comprehensive physical examination was performed was not captured consistently during the study period, we restricted our analysis to visits where a patient was seen by a provider, to minimize this possible bias.

Our results complement the few studies that have examined US trends in HPV and AGW prevalence. A 2006–2014 study assessed AGW trends among privately insured male and female individuals and found significant declines among girls and women aged 15–19 years (2008–2014), 20–24 years (2009–2014), and 25–29 years (2009–2014) and among men aged 20–24 years (2009–2014) [22]. We found additional significant declines in older groups, including women aged 30–39 years, MSW aged 25–39 years, and MSM aged >25 years. However, our study was conducted through 2016 and likely included publicly insured and uninsured patients. To better understand the burden of disease among larger segments of the population, future studies should include both uninsured and insured (publicly or privately) individuals in a variety of healthcare settings. Additionally, our observed declines in AGW prevalence among women compliment studies that used National Health and Nutritional Examination Survey data to document declines in the prevalence of quadrivalent HPV vaccine types from cervicovaginal specimens; one study documented declines in girls and women aged 14–24 years between 2003 and 2006 (the prevaccine era) and 2009–2012 (the postvaccine era) [31]. Our study found additional significant declines in women aged 25–39 years; however, comparison between these studies is difficult because our study captured only AGW, not HPV, prevalence and was conducted through 2016.

This study has several limitations. This study used data from STD clinics located in urban centers, limiting geographical representativeness. However, substantial diversity in patient demographic characteristics and the prevalence of AGW existed across jurisdictions. Interjurisdictional variations were adjusted for and therefore should not affect the reported trends in AGW prevalence. Second, linking patients across the full study period was not possible, so our study design would not preclude the inclusion of AGW cases in the same patients across multiple years. Also, since demographic and behavioral data were abstracted from medical records in each calendar year and because matching visits by unique patients was possible within years, cases with multiple visits in a year had more opportunities for more complete ascertainment of behavioral and/or demographic patient information (eg, the ability to be identified as MSM or MSW) when compared to patients with only 1 visit. However, the overall proportion of patients with missing information was low (ie, <5%) throughout the study period; therefore, this should have a minimal effect on trends. Last, our study lacked data on patients’ HPV vaccination status. This would be especially useful for elucidating the link between HPV vaccination status and AGW prevalence among groups that were age eligible for vaccination but have had historically low coverage rates. Vaccination information would also aid in understanding whether STD clinic patients are more or less likely to be vaccinated for HPV than the general population. Many STD clinics do not routinely vaccinate for HPV [32], although individuals may be vaccinated at other venues.

Despite these limitations, these data represent the first US evaluation of AGW trends among patients attending STD clinics. While patients attending STD clinics are not likely to represent all persons with AGW, they remain an important population with a higher burden of STIs [33]. The impact of STD prevention interventions may be more easily detected among such groups with higher STI morbidity. In conclusion, given the prophylactic efficacy and high population effectiveness of the HPV vaccine [34, 35] and that the age groups that were age eligible for the HPV vaccine experienced the sharpest decreases in AGW prevalence, it is likely that the observed decline in the proportion of patients attending STD clinics with AGW is partially the result of US implementation of HPV vaccination. However, our study is ecologic by design, and declines were observed in age groups that are not targeted for vaccination and are thus less likely to be affected, suggesting that other factors may be impacting observed trends. Continued surveillance for AGW can help monitor the impact of vaccination and other prevention and control activities.