Anogenital Warts Among Men With Human Immunodeficiency Viruses in Korea: A Single-Center Retrospective Study

Abstract

This retrospective study analyzed data from 1,192 men living with HIV (MWH) between 2002 and 2023, and identified 76 anogenital wart cases (6.4%), which were predominantly anal (n=67). Among 20 individuals with anal warts who underwent biopsy, 25% had high-grade squamous intraepithelial lesions (SILs). Of 15 individuals with low-grade SILs, one progressed to high-grade SIL after 5 years, and two developed anal cancer at 5 and 15 years. High-risk human papillomavirus genotypes were detected in 42.9% of tested specimens. These findings highlight the importance of routine screening and early detection of precancerous lesions in MWH in Korea.

Anogenital warts (AGWs) are common sexually transmitted infections caused by human papillomavirus (HPV), with most cases attributed to non-oncogenic low-risk (LR) HPV types 6 and 11. People living with human immunodeficiency viruses (HIV) (PWH), particularly men who have sex with men (MSM), are at higher risk of developing HPV-associated AGWs than HIV-negative individuals. PWH also have an elevated risk of infection with oncogenic high-risk (HR) HPV types, anal high-grade squamous intraepithelial lesions (HSILs), and anal cancers [1].

A history of AGWs in PWH is strongly associated with a significantly increased risk of anal cancer [2]. While AGWs are generally benign with low malignant potential, co-infection with HR-HPV is common among PWH and may increase the risk of HSILs and invasive cancer [3]. Notably, AGWs in PWH may harbor HSILs or even cancer despite appearing clinically as typical warts [4,5].

The ANCHOR trial demonstrated that screening and treating biopsy-confirmed anal HSILs significantly reduced progression to anal cancer in PWH [6]. Consequently, several clinical guidelines recommend routine anal cancer screening for PWH based on age and risk factors for the early detection and treatment of HSILs [5,7,8].

Previous studies have examined the epidemiology and burden of HPV-related diseases among PWH in Korea. Anal HR-HPV infection is more prevalent among MSM living with HIV (MSMWH) than among men who have sex with women (MSWWH) (47.4% vs. 25.0%) [9]. Furthermore, the proportion of HPV-associated cancers (HPVACs) has been increasing, with a median time from HIV diagnosis to the first HPVAC of 11.5 years [10]. In a recent cohort study, the incidence of AGWs among PWH in Korea was 10.85 per 1,000 person-years [11].

However, significant gaps remain in our understanding of the burden of HPV infection and the need for anal cancer screening among PWH in Korea. Barriers such as limited awareness, provider hesitancy, and financial constraints related to insurance coverage hinder routine screening implementation [12].

We examined men living with HIV (MWH) who presented with clinically diagnosed anal warts at a tertiary care hospital in Korea. Here, we describe the clinical characteristics of these individuals and evaluate the prevalence of anal cancer precursor lesions in patients who underwent biopsy.

We conducted a retrospective chart review of all MWH with AGWs and patients with other HPV-related diseases between 2002 and 2023. Clinical and demographic data, including treatment history, surgical interventions, and histopathological findings, were collected. Histopathological diagnoses were made according to the Lower Anogenital Squamous Terminology criteria, as recommended by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology [13]. Ki-67 and p16 immunohistochemical staining were used to evaluate dysplastic lesions. The highest-grade lesions were recorded when multiple histological grades were reported.

HPV genotyping data were obtained from surgical specimens or previous HPV testing [9]. Until September 2016, an HPV Genotyping Chip Kit (AGBIO Diagnostics, Seoul, Korea) was used; thereafter, a polymerase chain reaction-based assay (Anyplex II HPV28; Seegene, Seoul, Korea) was employed [14]. The observation period for individual patients started from their first visit to the study hospital after January 1, 2002, and continued until the earliest of the following dates: date of incident AGWs or anal cancer diagnosis, death, loss to follow-up, transfer to another institution, or December 31, 2023. The incidence of AGWs was calculated by dividing the number of incident AGW cases by person-time at risk and expressed as per 1,000 person-years (PY). The 95% confidence intervals (CIs) for incidence were calculated using the Poisson distribution.

Of the 1,192 MWH who visited the hospital between 2002 and 2023, 81 (6.8%) were diagnosed with AGWs (76 cases) or other HPV-related diseases (3 cases of head and neck cancer and 2 cases of anal cancer) (Fig. 1). Among the 76 patients with AGWs, the most common site of occurrence was the anus (n=67), followed by the penis (n=7), pubis (n=1), and the oral cavity (n=1). Based on the time of initial diagnosis, 23 cases were identified at the time of the initial visit: AGWs (n=22) and anal cancer (n=1). During the follow-up, 58 additional cases were identified, including AGWs (n=54), head and neck cancer (n=3), and anal cancer (n=1). The median observation period per patient was 4.3 years (interquartile range [IQR], 0.5–11.8), and the incidence rate of AGWs was 6.79 cases per 1,000 PY (95% CI, 5.1–8.86). By the end of 2023, of the 81 individuals, 66 remained under follow-up, 12 were transferred out or lost to follow-up, and 3 had died. Among the deaths, only 1 was related to an HPV-associated disease (tongue cancer).

Figure 1. A flowchart showing patient selection and clinical course.

HIV, human immunodeficiency viruses; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion.

Table 1 summarizes the baseline characteristics of 67 individuals with anal warts. The median age was 37 years (IQR, 26–50) and 97% of the individuals were MSM. At the time of AGW diagnosis, the median CD4+ cell count was 412 cells/mm (IQR, 225–601.3). Biopsies were performed in 20 individuals (29.9%), revealing HSILs in 5 (25.0%) and low-grade squamous intraepithelial lesions (LSILs) in 15 (75.0%). Among them, 1 initially diagnosed with LSIL progressed to HSIL, and 2 developed anal cancer at 5 and 15 years. One individual underwent four surgical excisions over 5 years, with cancer (T1N1M0, stage IIIa) diagnosed at the fourth excision and subsequently treated with chemotherapy and radiotherapy. The other was lost to follow-up for 6 years before being diagnosed with cancer (T1NxMx) via excision and subsequently treated with additional radiation therapy.

Table 1. Characteristics of 67 men living with HIV who presented with anal warts.

Characteristics		n	%
Median age, years (IQR)		37 (26–50)
	Age, ≤40	37	55.2
	Age, >40	30	44.8
Sexual behavior (N=67)
	MSM	65	97.0
	Non-MSM	2	3.0
Marital status (N=67)
	Single	47	70.1
	Married/ever married	19	28.4
	Unknown	1	1.5
History of injection drug use		3	4.5
CD4 count/µL (IQR)		412 (225–601.3)
	≤200	15	22.4
	201–500	26	38.8
	>500	26	38.8
HIV RNA ≤200 copies/mL (N=64)		38	59.4
History of anal warts		10	14.9
Timing of diagnosis
	At enrollment	23	34.3
	During follow-up	44	65.7
Site of anal warts
	Anorectal	64	95.5
	Anorectal + penile	3	4.5
Biopsy performed (N=20)
	LSIL	15	75.0
	HSIL	5	25.0
HPV test subgroup (N=21)
	High-risk HPV	9	42.9
	Low-risk HPV	13	61.9
	HPV 6 or 11	9	42.9a
Treatment (N=67)
	Non-surgical	17	25.4
	Surgical	24	35.8
	Both	5	7.5
	Not recorded	21	31.3
HPV vaccination
	Before presentation with anal warts	0	0
	After presentation with anal warts	5	7.5
HBV seropositive (N=65)		2	3.1b
HCV seropositive (N=65)		2	3.1b
Syphilis seropositive (N=67)		29	43.3b

^aTypes 6 and 11 are included in the low-risk HPV subgroup and are presented separately.

^bAny documented positive serology during the study period.

HIV, human immunodeficiency viruses; IQR, interquartile range; MSM, men having sex with men; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; HPV, human papillomavirus; HBV, hepatitis B virus; HCV, hepatitis C virus.

Of the 21 individuals who underwent HPV genotyping, 13 (61.9%) tested positive for LR-HPV and 9 (42.9%) for HR-HPV. Nine individuals (42.9%) tested positive for HPV types 6 or 11. The most common treatment modality was surgery (n=24; 35.8%). Non-surgical treatments, primarily imiquimod, were administered to 17 individuals (25.4%), with 5 (7.5%) subsequently requiring surgery following initial treatment failure.

In this study, 6.8% of MWH had AGWs, which were mostly symptomatic or incidentally detected during colonoscopy. Given the high prevalence of asymptomatic HPV infections and the likelihood of under-reporting, the true prevalence is probably higher. Anal warts were more common than those at other genital sites, likely reflecting the higher proportion of MSM among MWH. Korea’s national HPV vaccination program for adolescent girls may have contributed to the decline in the incidence of AGWs in women, potentially reducing transmission to men. National Health Insurance data from 2007 to 2019 showed that AGW prevalence in women increased until 2012 but decreased following vaccine implementation. In contrast, the prevalence continues to increase among men, particularly among those aged 20–49 years [15]. Moreover, the number of surgical procedures for anal warts in men increased 2.74-fold between 2010 and 2019, indicating an increasing HPV disease burden among Korean men [16].

MWH are associated with a significantly higher risk of anal cancer development than the general population [17,18]. This increased risk is largely attributable to the high prevalence of anal HR-HPV infections in MWH. A previous study in Korea reported HR-HPV prevalence rates of 47.4% and 25.0% in MSMWH and MSWWH, respectively [9]. Although HPV testing was performed in only 31.3% of MWH with anal warts, 42.9% tested positive for HR-HPV. Receptive anal intercourse is a key risk factor for anal cancer. According to 2023 data, 89.9% of newly diagnosed HIV cases in Korea were male, 56.7% were MSM, and 64.1% were aged 20–39 years [19], suggesting that the incidence of anal cancer among MWH is likely to increase.

In our cohort, 7.5% of 67 individuals initially diagnosed with anal warts had HSILs on biopsy. Among those initially diagnosed with LSILs, 1 developed HSILs and 2 were diagnosed with anal cancer, resulting in an overall HSIL or anal cancer rate of 11.9% among biopsied individuals. Without routine anal cancer screening, cases are typically detected only when biopsies are performed for atypical lesions, treatment failure, or diagnostic uncertainty. Because many HSIL cases are asymptomatic and biopsies are selective, the true prevalence may be underestimated.

These findings underscore the need for targeted anal cancer screening among MWH in Korea, particularly for screening and treating biopsy-confirmed HSILs, to prevent progression to anal cancer. However, significant barriers have prevented this from occurring. As of June 2025, anal cytology and high-resolution anoscopy were not covered by the Korean National Health Insurance because of the absence of specific billing codes. HPV genotyping is not reimbursed, which limits its accessibility and use in routine clinical care.

This study had several limitations. Because this was a retrospective, single-center analysis with a relatively small sample size, the findings may have been influenced by unmeasured confounding factors and may not be generalizable to other populations. Moreover, the study’s retrospective design may have limited data completeness and accuracy, affecting the estimates of AGW incidence among MWH. These limitations highlight the need for future multicenter prospective studies to validate our findings and assess the prevalence, progression risk, and cost-effectiveness of anal cancer screening strategies in this high-risk population.