1. 752 Diseases of the Colon & Rectum Volume 57: 6 (2014)
BACKGROUND: Men who have sex with men have
increased prevalence of both human papillomavirus and
anogenital condyloma.
OBJECTIVE: Risk factors for multiple treatment and
recurrence of anal condyloma were examined.
DESIGN: This is a retrospective study of HIV-negative
men who have sex with men who were treated for anal
condyloma.
SETTINGS: This study was conducted in a private surgical
practice.
PATIENTS: The patients were HIV-negative men who
have sex with men, aged 18 years or older.
INTERVENTION(S): Ablation with electrocautery or
CO2
laser was performed, as well as excision and topical
imiquimod condyloma treatment adjuvant.
MAIN OUTCOME MEASURES: Primary clearance, defined
as 4 months of condyloma-free survival posttreatment,
and recurrence, defined as any anal condyloma diagnosis
after primary clearance.
RESULTS: Of 231 participants, 207 achieved primary
clearance (median age, 32.0 years) and were followed
(median, 18.2 months) after primary treatment. Most
had intra-anal and perianal condyloma (56%), were
treated with electrocautery ablation (79.2%), and
required 1 treatment (range, 1–6) for clearance. There
were 57 recurrences (median, 12 months). One-third
each had minimal, moderate, or extensive disease.
Forty-six percent of patients received imiquimod
posttreatment adjuvant. High-grade dysplasia was found
in 31% at presentation and 43% during follow-up.
Factors associated with requiring multiple treatments
for clearance were participants having moderate disease
(adjusted odds ratio, 6.0 (1.7–21.4)) and receiving
imiquimod adjuvant (adjusted odds ratio, 4.7 (2.0–10.6)).
No single factor predicted recurrence, but those with
moderate disease experienced recurrences significantly
sooner (median, 25 months of follow-up).
LIMITATIONS: This was a retrospective chart review, it
was limited to a single practice, and it excluded those who
did not achieve primary clearance.
CONCLUSIONS: Most men who have sex with men have
intra-anal and perianal condyloma and concomitant
high-grade dysplasia is common. Most achieved clearance
with 1 treatment. Having both intra-anal and perianal
condyloma, increased severity of disease, and imiquimod
adjuvant were significant predictors of requiring multiple
treatments for clearance. No identified risk factors proved
a significant predictor of recurrence.
KEY WORDS: Condyloma; Men who have sex with men;
Anal; Human papillomavirus; Imiquimod; Human
papillomavirus vaccine.
H
uman papillomavirus (HPV) is the most com-
mon sexually transmitted infection in the United
States. An estimated 79 million Americans are
currently infected with HPV, and approximately 14 mil-
lion new infections occur each year.Anogenital condyloma
Anal Condyloma Treatment and Recurrence in
­HIV-negative Men Who Have Sex With Men
Richard J. Silvera, M.P.H.1
• Casey K. Smith, J.D.1
• Kristin A. Swedish, M.D., M.P.H. 2
Stephen E. Goldstone, M.D.3
1 Department of Medical Education, Icahn School of Medicine at Mount Sinai, New York, New York
2 Department of Medicine, Montefiore Medical Center, New York, New York
3 Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York
Dis Colon Rectum 2014; 57: 752–761
DOI: 10.1097/DCR.0000000000000080
© The ASCRS 2014
Funding/Support: Mr Silvera’s participation was funded by the Icahn
School of Medicine at Mount Sinai Summer Scholars Program. Dr
Smith’s participation was funded by a grant through a Clinical and
Translational Science Award from the NIH to the Icahn School of Medi-
cine at Mount Sinai. No other funding was received.
Financial Disclosure: None reported.
Presented at the meeting of the International Papillomavirus Confer-
ence, San Juan, Puerto Rico, November 30 to December 6, 2012.
Correspondence: Stephen E. Goldstone, M.D., 420 West 23rd St, New
York, NY 10011. E-mail: Goldstone.stephen@gmail.com
ORIGINAL CONTRIBUTION

2. Diseases of the Colon & Rectum Volume 57: 6 (2014) 753
caused by low-risk (LR) strains of HPV are estimated to
affect 1% of sexually active adults in the United States with
approximately 250,000 new cases diagnosed each year.1
A
study of the National Health and Nutrition Examination
Survey (NHANES) found that 5.6% of 18 to 59 year olds
reported ever having been diagnosed with genital condy-
loma.2
In addition, initial visits to clinicians in the United
States for treatment of genital warts almost doubled from
233,000 in 2001 to 453,000 in 2011. The incidence of ano-
genital condyloma in Canada also has been documented
to be increasing among men from 125/100,000 in 1985 to
150/100,000 in 2004.3,4
Studies have found that men who have sex with men
(MSM) demonstrate a higher prevalence of both high-
and low-risk anal HPV infections. A multicity study of
1218 HIV-negative MSM found a 57% prevalence of anal
HPV infection that did not vary by age (18-89 years) or
geographic location; LR HPV types 6 and 11, which are re-
sponsible for 90% of anogenital condyloma, were the sec-
ond and third most common strains.5
A large-scale study
found that the incidence of external genital lesions was
4.26 per 100 person-years among MSM compared with
1.39 per 100 person-years among heterosexual men.6
An-
other cross-sectional study found that HIV-positive MSM
had 2.2 increased odds of having anal condyloma than
HIV-positive heterosexual men.7
Clinicians use many different methods to treat anal
condyloma including ablation with cautery or laser, cryo-
therapy, and topical medications (applied either by the
patientortheclinician).8–10
However,recurrenceaftertreat-
ment is common. A study of 140 men and women treated
surgically for extensive perianal and intra-anal condyloma
reported a 25% recurrence rate within 12 months.11
An-
other study of patients presenting for surgical treatment
of extensive perianal and intra-anal condyloma reported a
40% recurrence rate.12
To date, research demonstrated that quadrivalent
HPV (qHPV) (Gardasil, Merck & Co, Inc) vaccination re-
duced the risk of high-grade squamous intraepithelial le-
sion (high-grade dysplasia, HSIL) recurrence after ablation
among vaccinated patients in comparison with nonvac-
cinated (OR, 0.5), but vaccination has not been shown to
have any effect on condyloma recurrence posttreatment.13,14
Given that reports of condyloma treatment efficacy
deal largely with heterosexual populations and rarely study
intra-anal disease, but in MSM both the incidence of LR
HPV anal infection and the burden of anal condyloma are
high, we endeavored to determine the effectiveness con-
dyloma treatment in a cohort of HIV-negative MSM and
identify factors that affect both cure rates and recurrence.
MATERIALS AND METHODS
This study represents a retrospective analysis of a pro-
spectively followed cohort treated for perianal and in-
tra-anal condyloma at a private surgical practice (S.G.)
between February 2008 and March 2012. To be included
in the study, patients had to be new patients to the prac-
tice, ­HIV-negative MSM with anorectal condyloma that
achieved primary clearance, and have at least 1 follow-up
visit at least 4 months after clearance. Primary clearance
wasdefinedasatleast4monthswithoutevidenceof 1)peri-
anal condyloma on physical examination or 2) ­intra-anal
condyloma on either standard or ­high-resolution anos-
copy (HRA).
Recurrence was defined as subsequent diagnosis of
perianal or intra-anal condyloma after achieving primary
clearance. The Icahn School of Medicine at Mount Sinai
Program for the Protection of Human Subjects approved
this study. In addition to course of treatment, medical re-
cords were abstracted for clinical presentation; smoking
history; history of chlamydia, gonorrhea, syphilis, or her-
pes infection; and monogamy at initial presentation.
For the purpose of analysis, condyloma were catego-
rized based on medical record descriptions and photo-
graphic documentation taken during HRA as 1) minimal:
scattered, small condyloma with prominent disease-free
areas; 2) moderate: widespread condyloma but with
­disease-free areas; or 3) extensive: circumferential or
­near-circumferential condyloma (Fig. 1). Treatment mo-
dalities used included excision, electrocautery ablation
(ECA), and CO2
laser ablation (laser). Treatment modality
was selected based on clinician recommendation and par-
ticipant preference. Excision and ECA occurred in-office,
whereas laser ablation occurred in the operating room.
Participants who received a complete 3-injection course
of qHPV vaccination before or during participation in this
study were considered vaccinated for this analysis.
Participants presenting to the practice for evalua-
tion of HPV-related anorectal disease were assessed by
digital anorectal examination, anal cytology, and standard
anoscopy. If insurance allowed, participants were tested
for oncogenic HPV by Hybrid Capture 2 (HC2) (Digene
Corporation, Gaithersburg, MD). Those with condyloma
and any other abnormality were evaluated with HRA as
previously described.15
In brief, during HRA the anal ca-
nal is stained with acetic acid, and the squamocolumnar
transformation zone and anal canal are examined with
magnification.We apply Lugol Iodine to better distinguish
low-grade squamous intraepithelial lesion ­(low-grade
dysplasia, LSIL) from HSIL. High-grade dysplasia and
anal squamous-cell cancer are typified by acetowhite,
Lugol-negative epithelium with vascular abnormalities
(mosaicism, punctuation, and atypical vessels), abnor-
mal glands, friability, ulceration, and mass effect. Lesions
suspicious for HSIL are biopsied for histology. We typi-
cally biopsy at least 1 wart in patients with condyloma but
absent lesions suspicious for HSIL. Condyloma were de-
fined based on visual appearance or pathology report. Flat
areas of LSIL without verrucous characteristics were not

3. SILVERA ET AL: CONDYLOMA AMONG HIV-NEGATIVE MSM754
treated or considered recurrence. Most disease was treated
­in-office with HRA-guided ECA or excision of small le-
sions. Large-volume disease that required an operating
room was treated with HRA-guided laser ablation.
Patients with moderate and extensive disease were ex-
amined twice at 6-week intervals posttreatment;those with
minimal disease were examined at 12 weeks posttreatment.
Follow-up included digital anorectal exam and standard
anoscopy. Thereafter, all patients were evaluated every 3
months for 1 year and then every 6 months for an addi-
tional year. All participants had anal cytology at 6-month
intervals; participants with abnormalities were evaluated
with HRA, and biopsies were collected as indicated. After
1 year, participants with normal cytology and no obvious
recurrence were seen yearly. Those with HSIL or flat LSIL
continued in follow-up as previously described.16
Recur-
rence was treated most often with HRA-guided ECA, or,
if limited and external, with either excision or imiquimod.
FIGURE 1. Condyloma classification. A, Minimal perianal condyloma with a small cluster (arrow). B, Minimal intra-anal condyloma with a
single lesion (arrow). C, Moderate perianal condyloma with multiple lesions scattered circumferentially around the verge but with significant
disease free areas. D, Moderate intra-anal condyloma with a large cluster lesion and a smaller single lesion (arrows). E, Extensive intra-anal
condyloma with almost complete circumferential involvement (arrows).

4. Diseases of the Colon & Rectum Volume 57: 6 (2014) 755
Participants with moderate and extensive perianal disease
were often treated with imiquimod as an adjuvant in the
hope of decreasing recurrence beginning approximately 2
weeks postablation (or once significant healing occurred)
for a 4-month course. Participants could undergo mul-
tiple treatments to clear disease in an effort to achieve the
primary end point of 4 months disease-free survival.
STATISTICAL METHODS
Quantitative variables are reported as median (range).
Categorical variables are reported as frequency (%) and
total n. Categorical variables were analyzed by using the
χ2
and Fisher exact tests and quantitative variables by us-
ing the Student t tests. A p value of <0.05 was considered
significant. Significant bivariates were entered into multi-
variable logistic regression, results of which were reported
as adjusted ORs (AORs), 95% CIs, and p values. An AOR
that did not include 1 or a p value of <0.05 was consid-
ered statistically significant. Finally, Kaplan-Meier curves
were prepared examining time from first treatment to re-
currence or end of follow-up. Participants were censored
either at first confirmed recurrence of anogenital condy-
loma or at last recorded follow-up visit. Factors were as-
sessed for significance in the Kaplan-Meier curve by using
a generalized Wilcoxon method. A p value <0.05 was con-
sidered significant.
RESULTS
We identified 313 HIV-negative MSM ≥18 years of age
with intra-anal and perianal condyloma seen between
February 2008 and March 2012 (Fig. 2). Eighty MSM were
excluded because they did not have adequate follow-up
postprimary ablation. An additional 2 were excluded be-
cause they were treated solely with imiquimod and not an
ablative technique, leaving 231 evaluable for clearance and
recurrence. Of these MSM, 207 (89.6%) achieved primary
clearance, and their characteristics are detailed in Table 1.
Table 2 details characteristics of the 24 patients (10.4%)
who did not achieve primary clearance.
Participants who cleared had a median age of 32.0
(range, 19.7-73.8) years and were followed for a median
of 18.2 (3.2-54.1) months after primary treatment. Be-
fore referral to the practice, 126 (60.9%) participants had
a previous history of condyloma treatment, most often
with either clinician- or patient-applied topical therapies
or cryotherapy. The most common presentation was both
intra-anal and perianal condyloma found in 117 partici-
pants (56%), with an even distribution of minimal, mod-
erate, and extensive disease. Electrocautery ablation was
the initial therapy in 164 (79.2%) participants, 34 (16.4%)
required laser treatment in the operating room, and 9
(4.3%) were treated with excision. Duration of treatment
ranged from 0 to 42.3 months with a mean of 2.2 months;
median, 0 months. The median number of treatments re-
quired for clearance was 1 (range, 1-6). Imiquimod was
used as a posttreatment adjuvant in 112 (46.4%) par-
ticipants. Quadrivalent HPV vaccine was not used ther-
apeutically but was offered to many patients as off-label
immunization, and 135 (64.6%) received it at some point
either before or during the study. In addition to condy-
loma, HSIL was found in 64 (30.9%) participants at initial
presentation and in 88 (42.5%) during follow-up. No par-
ticipant had anal cancer.
One hundred fifty-five participants (74.9%) expe-
rienced clearance after a single treatment. The median
time to clearance was 0 (range, 0-42.3) months. Partici-
pants requiring more than 1 treatment were more likely to
have both perianal and intra-anal condyloma (p = 0.001),
more extensive initial presentation (p < 0.001), or to
have received imiquimod as a posttreatment adjuvant
(p < 0.001). Treatment method did not affect the number
HIV-negative MSM age > 18
with anogenital condyloma
n = 313
Excluded:
• Inadequate follow-up:
n = 80
• Primary treatment
with imiquimod: n = 2
Evaluable for primary
end point: n = 231
Achieved primary
clearance: n = 207
No primary clearance:
n = 24
FIGURE 2. Study flow chart. MSM = men who have sex with men.

5. SILVERA ET AL: CONDYLOMA AMONG HIV-NEGATIVE MSM756
of treatments needed for clearance, nor did patient age or
receiving qHPV (Table 1).
Table 3 presents factors associated with requiring more
than 1 treatment for clearance with multivariable analysis.
Moderate condyloma at presentation had an AOR of 5.9
(95% CI, 1.7-20.7), extensive condyloma had an AOR of 1.3
(95% CI, 0.62-2.8), as well as receiving imiquimod as an ad-
juvant with anAOR of 4.1 (95% CI,1.8-9.0).Moderate con-
dyloma severity and imiquimod adjuvant were significantly
associated with each other (p = 0.03) and, therefore, may be
confounders rather than independent variables associated
with requiring multiple treatments for clearance.
Recurrence postclearance occurred in 57 partici-
pants after a median time from their first treatment of
11.7 (range, 5.9-48.3) months. Kaplan-Meier curves of
time to recurrence from first treatment for those with
minimal, moderate, and extensive disease are shown in
Figure 3. Probability of recurrence at 1 year was 9.9%
(95% CI, 0-22.4) for those with minimal disease, 19.5%
(95% CI, 2.5-36.4) for those with moderate disease, and
15.3% (95% CI, 0-40.8) for those with extensive disease.
The probability of recurrence increased to 14.1% (95%
CI, 3.8-24.4), 29.9% (95% CI, 18.2-41.6), and 20.3%
(95% CI, 0.3-40.3) at 2 years and to 15.5% (95% CI, 6.3-
24.7), 32.5% (95% CI, 21.2-43.8), and 28.1% (95% CI,
14.3-43.4%) at 3 years for those with minimal, moderate,
and extensive disease. The estimated median time to re-
currence from first treatment for minimal and extensive
TABLE 1. Traits associated with recurrence and multiple treatment events for primary clearance
Total
(n = 207)
Recurrence
(n = 57)
No recurrence
(n = 150) p
1 Treatment for
clearance (n = 155)
>1 Treatment for
clearance (n = 52) p
Age, y, median (range) 32.0 (19.7–73.8) 32.4 (20.2–73.8) 31.9 (19.7–71.4) NS 33.0 (19.7–73.8) 30.9 (20.2–56.9) NS
Duration of follow-up,
mo, median (range)
18.2 (3.2–54.1) 24.0 (6.2–54.1) 16.6 (3.2–49.8) 0.003 17.0 (3.2–50.8) 21.9 (6.6–54.1) 0.020
Time to primary
clearance, mo,
median (range)
0 (0–42.3) 0 (0–37.6) 0 (0–42.3)
NS
0 (0–6.7) 4.9 (1.2–42.3) <0.001
History of smoking
Yes 16.4% (34) 14.0% (8) 17.3% (26)
NS
18.1% (28) 11.5% (6)
NS
No 83.6% (173) 86.0% (49) 82.7% (124) 81.9% (127) 88.5% (46)
Monogamous at visit 1
Yes 30.9% (64) 31.6% (18) 30.7% (46)
NS
30.3% (47) 32.7% (17)
NS
No 69.1% (143) 68.4% (39) 69.3% (104) 69.7% (108) 67.3% (35)
Location of presenting condyloma
Perianal 9.7% (20) 5.3% (3) 11.3% (17)
NS
9.7% (15) 9.6% (5)
0.001 Intra-anal 34.3% (71) 31.6% (18) 35.3% (53) 41.3% (64) 13.5 (7)
Both 56.0% (116) 63.2% (36) 53.3% (80) 49.0% (76) 76.9% (40)
Severity of condyloma
Minimal 34.3% (71) 22.8% (13) 38.7% (58)
NS
41.9% (65) 11.5% (6)
0.001 Moderate 37.2% (77) 43.9% (25) 34.7% (52) 34.2% (53) 46.2% (24)
Extensive 28.5% (59) 33.3% (19) 26.7% (40) 23.9% (37) 42.3% (22)
Initial condyloma treatment
Excision 4.3% (9) 1.8% (1) 5.3% (8)
NS
5.2% (8) 1.9% (1)
NS Electrocautery 79.2% (164) 84.2% (48) 77.3% (116) 79.4% (123) 78.8% (41)
CO2
laser 16.4% (34) 14.0% (8) 17.3% (26) 15.5% (24) 19.2% (10)
Total treatment events
for clearance, median
(range)
1.0 (1–6) 1.0 (1–6) 1.0 (1–6)
NS
1.0 (1–1) 2.0 (2–6)
N/A
History of STI (gonorrhea, chlamydia, or syphilis)
Yes 27.5% (57) 26.3% (15) 28.0% (42)
NS
28.4% (44) 25.0% (13)
NS
No 72.5% (150) 73.7% (42) 72.0% (108) 71.6% (111) 75.0% (39)
Any oncogenic HPV
Yes 58.0% (120) 59.6% (34) 57.3% (86)
NSa
62.6% (97) 44.2% (23)
NSa
No 24.6% (51) 26.3% (15) 24.0% (36) 24.4% (38) 25.0% (13)
Not tested 17.4% (36) 14.0% (8) 18.7% (28) 12.9% (20) 30.8% (16)
Quadrivalent HPV vaccination
Yes 64.3% (133) 68.4% (39) 62.7% (94)
NS
61.3% (95) 73.1% (38)
NS
No 35.7% (74) 31.6% (18) 37.3% (56) 38.7% (60) 26.9% (14)
Imiquimod adjuvant used in treatment
Yes 46.4% (96) 52.6% (30) 44.0% (66)
NS
36.1% (56) 76.9% (40)
0.001
No 53.6% (111) 47.4% (27) 56.0% (84) 63.9% (99) 23.1% (12)
STI = sexually transmitted infection; HPV = human papillomavirus.
a
Excluding participants“not tested.”

6. Diseases of the Colon Rectum Volume 57: 6 (2014) 757
disease did not significantly differ and was 48.3 (95% CI,
32.0-64.5) months but 24.0 (95% CI, 19.6-28.5) months
for those with moderate disease.
Neither age, smoking history, monogamy, location or
severity of condyloma, requiring more than 1 treatment
for primary clearance, total number of treatments, history
of oncogenic HPV, treatment modality, sexually transmit-
ted infection history, receiving qHPV, or imiquimod adju-
vant proved a significant predictor of recurrence. Survival
analysis considered all recorded variables,including smok-
ing history, monogamy, high-risk HPV infection, location
of presenting condyloma, history of sexually transmitted
infection, receiving qHPV, and severity of presenting con-
dyloma. Only severity of presenting condyloma was sig-
nificantly associated with time to recurrence (p = 0.001;
other data not shown).
The 24 MSM that did not achieve primary clearance
differed significantly from those that did with respect to
the fact that they had a shorter duration of follow-up (me-
dian, 6.1 (range, 4.1-18.6) months [p 0.001]), were less
likely to have only intra-anal condyloma (4.2%, p = 0.008),
less likely to receive qHPV (29.2%, p = 0.001), but more
likely to receive imiquimod as a postablation adjuvant
(70.8%, p = 0.03; Table 2). Factors associated with failing
to achieve primary clearance with multivariable analysis
TABLE 2. Traits associated with failure to achieve primary clearance
Characteristic Total (n = 24) Bivariate p
Multivariate analysis
AOR p
Age, y, median (range) 29.6 (20.7–57.8) NS
Duration of follow-up, mo, median (range) 6.1 (4.1–18.6) 0.001 1.3 (1.1–1.5) 0.001
History of smoking
Yes 25.0% (6)
NS
No 75.0% (18)
Monogamous at visit 1
Yes 29.2% (7)
NS
No 70.8% (17)
Location of presenting condyloma
Perianal 20.8% (5)
0.008
1 -
Intra-anal 4.2% (1) 29.7 (2.6–341.9) 0.007
Both 75.0% (18) 2.9 (0.63–12.9) 0.172
Severity of condyloma
Minimal 37.5% (9)
NS Moderate 45.8% (11)
Extensive 16.7% (4)
Initial condyloma treatment
Excision 8.3% (2)
NS Electrocautery 75.0% (18)
CO2
laser 16.7% (4)
Total treatment events, median (range) 2.0 (1.0–5.0) NS
History of STI (gonorrhea, chlamydia, or syphilis)
Yes 45.8% (11)
NS
No 54.2% (13)
Any oncogenic HPV
Yes 58.3% (14)
NS No 12.5% (3)
Not tested 29.2% (7)
Quadrivalent HPV vaccination
Yes 29.2% (7)
0.001
5.8 (1.8–18.0) 0.003
No 70.8% (17) 1 -
Imiquimod adjuvant used in treatment
Yes 70.8% (17)
0.03
0.27 (0.07–1.0) 0.051
No 29.2% (7) 1 -
AOR = adjusted odds ratio; STI = sexually transmitted infection; HPV = human papillomavirus.
TABLE 3. Multivariable logistic regression for 1 treatment for
clearance vs 1 treatment for clearance
AOR (95% CI) p
Location of presenting condyloma
Perianal 1 -
Intra-anal .4 (0.01–1.7) 0.209
Both perianal and intra-anal 1.0 (0.33–3.1) 0.976
Severity of presenting condyloma
Minimal 1 -
Moderate 6.0 (1.7–21.4) 0.006
Extensive 1.4 (0.66–3.1) 0.365
Imiquimod adjuvant
Yes 4.7 (2.0–10.6) 0.001
No 1 -
AOR = adjusted odds ratio.

7. SILVERA ET AL: CONDYLOMA AMONG HIV-NEGATIVE MSM758
were the shorter duration of follow-up (AOR, 1.3; 95%CI,
1.1-1.5), being less likely to just have intra-anal condyloma
(AOR, 29.7; 95% CI, 2.6-341.9), and not receiving qHPV
(AOR, 5.8; 95% CI, 1.8-18.0).
The 80 participants that were excluded because of
inadequate follow-up did not significantly differ from
included patients with respect to age, monogamy, smok-
ing status, history of oncogenic HPV, treatment modal-
ity, sexually transmitted infection history, or receiving
qHPV (data not shown). They were, however, significantly
less likely to have both intra-anal and perianal disease
(p = 0.001).
DISCUSSION
This study shows that requiring multiple treatment events
to achieve primary clearance of anogenital condyloma is
associated with increased severity of disease and the use
of an imiquimod as posttreatment adjuvant. Although no
factors were significantly associated with posttreatment
condyloma recurrence, participants with moderate sever-
ity of disease developed recurrence in a significantly short-
er time from the first treatment than those with minimal
or extensive disease.
Many strategies have been used to address the rising
rates of HPV infection and condyloma, but it remains
a concern, particularly for MSM. Quadrivalent HPV
­vaccine has been shown to decrease anogenital condyloma
in MSM, but male vaccination rates remain low.6,14
Since
2011, when qHPV vaccination guidelines were expanded
to include males, only an estimated 8.3% of males aged
13 to 17 years were vaccinated.17
It follows that anogeni-
tal condyloma will remain a significant health burden for
MSM until vaccination rates increase among this popu-
lation. Our data illustrate the crucial point that condy-
loma in MSM most often involve both the perianal and
­intra-anal areas. Therefore, clinicians treating MSM
with visible external condyloma must be sure to rule out
­intra-anal disease. Large-scale studies are still needed to
determine the effect of qHPV vaccination on condyloma
recurrence.
Another barrier to successful treatment of ­intra-anal
condyloma is that there are no Food and Drug
­Administration-approved patient-applied topical thera-
pies available. These barriers suggest that new treatments
or prevention strategies are needed to address condyloma
among MSM. In our hands, ECA was the preferred treat-
ment modality for perianal and intra-anal condyloma for
several reasons. The vast majority of patients achieved
clearance with a single ECA treatment. Moreover, ECA
allows full-thickness destruction of condyloma in a sin-
gle treatment. Conversely, treatment with imiquimod or
cryotherapy often requires multiple treatments over pro-
longed periods.10
Cryotherapy and topical agents produce
variable depths of necrosis, necessitating repeated treat-
ments separated by an interval to allow for healing, es-
pecially when treating bulky, hyperkeratotic condyloma.
Knowing that we had achieved full-thickness destruction
allowed us to feel comfortable not seeing participants after
ECA for 6 to 12 weeks. Those treated with cryotherapy or
topical agents are often seen at 2- to 3-week intervals for
possible re-treatment.
The primary drawback for ECA is the requirement of
local anesthetic, which is not necessary for either cryother-
apy or clinician-applied topical agents.18–24
In our view, the
greater likelihood of achieving clearance after just 1 treat-
ment makes ECA the better approach. Although pain and
other morbidities like bleeding might be greater with ECA
in comparison with other less extensive treatments, we be-
lieve the benefit derived from fewer visits make it the bet-
ter approach. Clearly, those who have extensive disease are
best treated in the operating room where the goal of either
laser or cautery ablation is also to produce full-thickness
destruction of the condyloma.
Approximately one-fourth of patients required mul-
tiple treatments to achieve clearance. As would be expect-
ed, those with the most extensive disease were statistically
more likely to require multiple treatments to clear.Surpris-
ingly, having both intra-anal and perianal condyloma did
not significantly affect the need for multiple treatments
in multivariable analysis. Imiquimod as a posttreatment
adjuvant was significantly associated with requiring more
1.0
Cumulative survival
Condyloma serverity
Minimal
Moderate
Extensive
0.8
0.6
0.4
0.2
0 6 12 18 24
# at risk
30 36 42 48
71 59 33 20 16 11 6 3 1
77 68 43 24 12 7 7 4 0
59 58 47 40 34 24 15 6 2
Minimal
Moderate
Extensive
FIGURE 3. Kaplan-Meier survival analysis of time from first
treatment to recurrence by severity of presenting condyloma.

8. Diseases of the Colon Rectum Volume 57: 6 (2014) 759
than 1 treatment for clearance, but had no effect on re-
currence after achieving primary clearance. Some studies
have shown that posttreatment imiquimod as an adjuvant
reduces recurrence in both men and women with ano-
genital condyloma.25–27
On the surface, our data, however,
seem contradictory. An explanation for this seemingly op-
posite finding is that imiquimod use in our cohort was
significantly associated with the severity of disease, and,
as such, our results likely reflect imiquimod as a proxy for
more significant disease, rather than an independent fac-
tor for causing recurrence. Further study is necessary to
determine the true relationship between imiquimod and
recurrence.
Almost one-third of patients who achieved clearance
had a recurrence, a rate that is similar to rates reported in
other series.10–12,28
It is noteworthy that the median time
from first treatment to recurrence was more than 2 years;
some patients did not have a recurrence until 3 or more
years. Some “recurrence” may be related to new infection
rather than to the recurrence of disease present at the time
of primary therapy; we cannot determine if this was in-
deed the case, because our data did not capture whether
participants who had a later recurrence differed in sexual
practices or numbers of partners than those who did not
have a recurrence.
Our data did not identify any significant variable as-
sociated with recurrence, including severity or location of
disease, or method of treatment. Other series have associ-
ated smoking with recurrence, but we did not find that to
be the case.29
Our data also did not show that those with
the most extensive disease or requiring multiple treat-
ments to achieve primary clearance were the most likely
to have a recurrence and may be due to assumptions made
in our study design: specifically, that we did not begin cal-
culating recurrence until patients were clear for 4 months.
Moreover, the multiple treatments required by some
(those with more extensive disease and with both perianal
and intraanal condyloma) could actually have been treat-
ing recurrent rather than primary disease. If this is the
case, then our data actually show that there are no obvi-
ous variables affecting recurrence once a patient has been
disease free for 4 months.
Although it would seem intuitive that participants
with minimal disease would take longer to have a re-
currence than those with more extensive disease, our
­Kaplan-Meier curves of time to recurrence show no dif-
ference in time to recurrence for those with minimal and
extensive disease, and those with moderate disease had
significantly faster recurrences and were more likely to re-
quire more than 1 treatment to achieve primary clearance
(Fig. 3). This finding may be a reflection of the somewhat
subjective method by which we grouped patients based on
disease severity, and some classified as moderate disease
might actually have had extensive disease. Another possi-
ble explanation is that those with extensive disease had cir-
cumferential or near-circumferential ablation. This more
extensive ablation might have decreased recurrence over
those with only moderate disease where condyloma-free
skip areas were not treated. Leaving areas untreated might
have predisposed these patients to recurrence because of
less aggressive therapy. Further study is necessary to an-
swer this question. Moreover, it would be ideal to develop
and validate a more exact measurement for reporting se-
verity of disease in future investigations.
In addition, as demonstrated in other studies, our
data support that HIV-negative MSM with condyloma are
at risk for HSIL, an anal cancer precursor.15,30
Our findings
reinforce the importance of evaluating patients with con-
dyloma for HSIL with HRA and biopsy of areas suspicious
for HSIL. Condyloma must be viewed as a marker of HPV
infection—both LR and oncogenic HPV.
It is difficult to draw definitive conclusions from our
data regarding factors associated with failure to achieve
primary clearance postablation given the small number of
participants that fell into this category. That said, it ap-
pears that shorter duration of follow-up and not receiv-
ing qHPV could make patients less likely to clear. With
only 1 participant who did not achieve clearance having
just intra-anal condyloma, it is dangerous to apply much
import to that as a significant trait associated with failure
to clear. More study needs to be done with a much larger
sample size and longer follow-up to determine what char-
acteristics, if any, are associated with the inability to clear
condyloma.
This study has a number of limitations in addition
to those already mentioned. First, it is a retrospective
analysis of prospectively collected data in a highly select
group of MSM treated by a surgeon experienced in treat-
ing ­HPV-related anorectal disease; as such, the data might
not be generalizable to other populations. The analysis
also excluded patients who did not achieve primary clear-
ance and those who had inadequate follow-up, and these
patients significantly differed from patients who were ana-
lyzed in 2 key ways. Additionally, this analysis combined
those who received qHPV before treatment and those who
received qHPV concurrent with treatment into a single
group that may have obscured differences between those
2 groups. Further, flat LSIL was also not included in the
analysis and this could have caused an underestimation
of recurrence. The time interval between wart appearance
and the initiation of treatment was not evaluated, because
it is highly subjective. There is no way to know how long
a patient had disease before it was actually identified. The
interval between disease appearance and treatment may
have influenced disease severity, treatment effectiveness,
or recurrence. Additionally, our classification of lesions
by visual inspection constitutes a subjective variable that
may have affected our final analysis. Finally, data regarding
smoking history and sexual practices were only collected
at the initial visit, and, based on our data, we cannot evalu-

9. SILVERA ET AL: CONDYLOMA AMONG HIV-NEGATIVE MSM760
ate how changes in those habits may affect treatment or
recurrence.
The strengths of this study include the fact that it
is one of the few to examine the efficacy of condyloma
treatment in MSM with anal canal disease. Moreover, the
lengthy follow-up can give a truer estimate of probabil-
ity of recurrence than most studies with a much shorter
follow-up.
CONCLUSION
Most HIV-negative MSM with anorectal condyloma can
achieve primary clearance with 1 treatment with the use
of laser or cautery ablation. Those with more extensive
disease are more likely to require multiple treatments to
achieve clearance. Approximately one-third of patients
treated had a recurrence, but the time to recurrence was
long. No obvious variables affecting recurrence were
identified.
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