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Joetal. BMC Urol (2021) 21:13
https://doi.org/10.1186/s12894-020-00777-1
RESEARCH ARTICLE
Optimal treatment forpenile verrucous
carcinoma: asystematic literature review
Dong In Jo1 , Song Hyun Han1, Soon Heum Kim1, Hye Young Kim2, Hong Chung3 and Hong Sup Kim3*
Abstract
Background: Verrucous carcinoma, a rare low-grade well-differentiated squamous cell carcinoma, is known for its
favorable biological behavior and lack of metastatic potential. However, aggressive resection is problematic in terms
of compromised function and aesthetics. Hence, more conservative treatments are needed. Methods: To identify the
up-to-date general biological behavior, diagnosis, and treatment trends, we searched PubMed using the keyword
“penile verrucous carcinoma” without restrictions on publication date. Results: Current treatments for penile verrucous
carcinoma include wide surgical excision, seldom preventive lymphadenectomy, and conservative chemotherapy
without surgery or local excision with safe margins. Despite the advent of partial penectomy to minimally impact
function and aesthetics, affected patients experience psychosexual problems. Local excision can be used to save the
penile shaft and glans penis without preventive lymphadenectomy or adjuvant therapy and can achieve good clinical
prognosis with rare recurrence. Conclusions: To preserve the functional and cosmetic aspects, we recommend local
excision, especially for tumors measuring < 3 cm and classified as stage T1 according to the 2016 tumor node metas-
tasis clinical and pathological classification for penile cancer.
Keywords: Local excision, Penile verrucous carcinoma, Squamous cell carcinoma
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Background
Verrucous carcinoma, a rare low-grade well-differen-
tiated squamous cell carcinoma (SCC), is known for its
slowly compressive expanding warty growth and rare
metastasis [1–3]. Aggressive treatment, such as penec-
tomy, has been suggested based on the concept that
penile verruca carcinoma (PVC) is malignant. In con-
trast, less aggressive treatment, such as local excision
without preventive lymphadenectomy, has been sug-
gested based on the concept that the biological behavior
of PVC resembles that of a benign tumor. In patients who
had undergone aggressive wide surgical excision of the
glans penis and penile shaft, many functional, cosmetic,
and psychosexual problems have been reported. To date,
surgical treatment trends have been unclear regarding
the use of preservation surgery. Here we reviewed the
literature to determine the most effective treatment for
PVC and suggest best practices for treatment guidelines.
Methods
To summarize the prevalence, causative factors, diag-
nostic methods, treatment methods, clinical behaviors,
diagnostic imaging techniques, and prognosis of PVC,
we searched PubMed for relevant studies using the key-
word “penile verrucous carcinoma” without restrictions
on publication year and retrieved abstracts published in
English that mentioned PVC diagnosis and treatment.
e abstracts were screened according to inclusion and
exclusion criteria. e inclusion criteria were presented
cases and the corresponding treatment methods, micro-
scopic diagnosis of PVC, availability of full text articles,
and publication in English. e exclusion criteria were
lack of tumor staging information and tumor staging
beyond T2 (Stage T2 penile cancers are different from
penile verrucous carcinoma and defined as invasive
Open Access
*Correspondence: hskim@kku.ac.kr
3 Department of Urology, Konkuk University School of Medicine,
Gukwon-daero 82, 27376 Chungju, Chungbuk, Republic of Korea
Full list of author information is available at the end of the article
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Page 2 of 14
Joetal. BMC Urol (2021) 21:13
cancers such as squamous cell carcinoma and others).
To check the association between treatment method and
conditions of cases, the treatments were categorized into
2 groups—the less aggressive treatment group included
shaving, local excision, and no surgery and the aggressive
treatment group included glansectomy, partial penec-
tomy, and total penectomy. Individual factors included
age, case history, tumor size, tumor shape, tumor loca-
tion, tumor stage, adjuvant treatment, lymph node
metastasis, disease-free status, recurrence, human papil-
loma virus (HPV) infection status, and treatment trends
over time.
e statistical analysis was performed using SPSS for
Windows version 25 (SPSS Inc., Chicago, IL, USA). We
hypothesized that aggressive treatment is more effec-
tive and investigated the difference in efficacy between
the 2 treatments. We performed a t-test, a chi-squared
test, and Fisher’s exact test to ensure data accuracy and
a regression analysis to examine whether the individual
factors were correlated in the 2 groups.
Results
A total of 276 articles were retrieved from PubMed.
Among them, 68 abstracts that mentioned PVC diag-
nosis and/or treatment and were published in English
were selected. e studies were published between 1969
and February 2019. Most of the studies were published
in English; other publication languages included Span-
ish (14), Chinese (3), French (3), Japanese (2), Bulgarian
(1), Israeli (1), and Italian (1). Several studies mentioned
regarding PVC treatment and were simple case reports
[4–47]. Its rarity is supported by the fact that 1 case in
a 10-year period and 13 cases in a 30-year period were
reported [10, 48–51]. Among the 68 studies retrieved,
28 met the inclusion criteria. Of those, 9 were excluded
according to the exclusion criteria. us, a total of 19
studies were subjected to full-text review (Fig. 1) [4–7,
10, 11, 20, 23, 31, 32, 35, 37–40, 43, 45–47].
e studies comprised a total of 58 cases of PVC
(Table1). e patients were 28–86years of age. e case
histories were 1–204months long. e tumor sizes were
0.8–10cm. Fifty-4 of the cases included a description of
tumor shape: papillary cauliflower in 30, keratotic horn-
like in 3, and warty verrucous in 21. e tumors involved
the glans in 33 cases, coronoid sulcus in 4, shaft in 4,
prepuce in 7, prepuce and glans in 4, glans and coro-
noid sulcus and shaft in 1, prepuce and coronoid sulcus
in 2, glans and coronoid sulcus in 2, and coronoid sulcus
and shaft in 1. A total of 10 cases involved the coronoid
sulcus, an area in which penile carcinoma would more
rapidly infiltrate the penile fascia. Regarding staging, 52
cases were classified as stage Ta, 4 were classified as T1,
and 2 were classified as T1a. Regarding treatment, no
surgery was performed in 4 cases, local excision was per-
formed in 10, shaving in 3, Mohs surgery was performed
in 2, circumcision was performed in 1, glansectomy was
performed in 3, partial penectomy was performed in
29, and total penectomy was performed in 6. us, 20
cases involved less aggressive treatment and 38 cases
involved aggressive treatment. Fifteen cases of adjuvant
treatment were reported, including 1 of radiotherapy, 6
of chemotherapy, 2 of chemoradiotherapy, and 6 of local
therapy (CO2 laser, cryotherapy, intralesional interferon,
and topical fluorouracil). ere was only 1 case of lymph
node metastasis. e reported lymphadenopathies were
revealed as inflammation without metastasis [4–6]. One
case of bilateral lymph node metastasis, which was sus-
pected as a mixed tumor condition with moderately
differentiated SCC, was reported [35]. e follow-up
period was 6–228months (19years). ere were 7 cases
of tumor recurrence: 5 in the less aggressive treatment
group and 2 in the aggressive treatment group. All cases
except 2 achieved tumor-free status. e other 2 patients
died due to other malignant conditions [35, 47]. Six
cases were associated with the following diseases: ana-
plastic spindle cell carcinoma suggestive of malignant
transformation after radiotherapy, hybrid verrucous
SCC, moderately differentiated SCC, lichen sclerosis,
pseudoepitheliomatous keratotic and micaceous balani-
tis, and human immunodeficiency virus infection. HPV
infection status was described as negative in 8 cases; the
others were not specified. e reported cases follow-
ing the year of issue categorized in 10-year increments:
1 in the 1970s, 14 in the 1980s, 2 in the 1990s, 15 in the
2000s, and 26 in the 2010s. e main diagnostic method
was biopsy. Chest x-ray, HPV polymerase chain reaction
(PCR), ultrasonography, and computed tomography were
optional. e best diagnostic method was biopsy and
HPV PCR. Ultrasonography, computed tomography, and
magnetic resonance imaging (MRI) offered more precise
information about tumor anatomy and regional lymphad-
enopathy. Two reports mentioned surgical treatment
guidelines according to tumor size [8] and depth [17].
Concerning surgical excision, the main treatment was
radical surgery, including at least partial penectomy [4–
47], even with the relatively small tumor size (< 3cm) [8].
e surgical margins were 2cm in cases of partial penec-
tomy and 0.3–1cm in cases of local excision (Table2) [5,
6]. In contrast, some studies have emphasized the good
clinical results of local excision because of the favorable
clinical behavior of PVC [5, 6, 11, 15, 17, 31, 32, 37, 39,
40, 43, 45–47].
e results of the t-test using categories of age, case
history, and tumor size and the result of the cross-sec-
tional analysis of the categories of tumor shape, disease-
free status, and HPV status were excluded since some
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Page 3 of 14
Joetal. BMC Urol (2021) 21:13
individual data for each case were missing (data not
shown). In the cross-sectional analysis, tumor location,
tumor stage, and recurrence were not significantly associ-
ated with either treatment. Regarding the clinical results,
all but 2 patients (who died of other malignant condi-
tions) achieved disease-free status. Regarding treatment
efficacy, the recurrence rates did not differ significantly
between the less aggressive and aggressive treatments.
Patients who received adjuvant therapy tended to ulti-
mately receive less aggressive treatment. Regarding the
test statistics, the X2 was 21.926 and the probability was
0.000. us, the results were statistically significant.
Regarding differences in treatment trends over time, the
X2 was 12.549 and the probability was 0.005. us, the
result was statistically significant (Table3).
Fig. 1 The study flow chart
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Joetal. BMC Urol (2021) 21:13
Table 1 Clinical manifestations ofpenile verrucous carcinoma
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
1(47) 49 12 5 × 4.5 x 2 Papillary
cauli-
flower
Glans,
coronoid
sulcus,
Ta local exci-
sion Systemic
bleo-
mycine,
metho-
trexate,
none 48/no 24 Anaplastic
spindle
cell carci-
noma
Negative 1994
shaft Radiother-
apy Malignant
transfor-
mation
after
Radio-
therapy
2(46) 62 3 3 Cauliflower-
like Prepuce,
coronal
sulcus
Ta Local exci-
sion None None 54/yes 26 Hybrid
verrucous-
squamous
cell carci-
noma
Negative 2000
3(45) 42 4 7 Cauliflower-
like Prepuce,
glans Ta Local exci-
sion CO2 laser None 36/yes None None ? 2008
4(43) 51 24 ? Verrucous Glans,
coronary
sulcus
Ta Recurred
mass Liquid
nitrogne,
topical 5%
fluoro-
uracil
None 42/yes None None ? 1978
after local
excision
and skin
graft
after local
excision
5(40) 60 ? ? ? Glans Ta Shaving Intralesional
interfer-
one
None 30/yes None None Negative 2000
6(39) 69 24 1 Keratotic Glans Ta Shaving Cryosurgery
with liquid
nitrogen
None 36/yes None None ? 2002
7(39) 69 24 1.5 Keratotic Glans Ta Shaving Cryosurgery
with liquid
nitrogen
None 36/yes None None ?
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Joetal. BMC Urol (2021) 21:13
Table 1 (continued)
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
8(38) 27 12 5 × 5 Verrucous gLans Ta None Intra-aortic
infusion
with
metho-
trexate
None 214/yes None None ? 2003
9(38) 65 3 4 × 3 Warty Glans Ta None Intra-aortic
infusion
with
metho-
trexate
None 165/yes None None ?
10(38) 31 48 5 × 5 ? Shaft Ta Total penec-
tomy Intra-aortic
infusion
with
metho-
trexate
None 149/yes 36/partial None ?
due to
partial
response
Response
and unbara-
ble pain
11(38) 75 120 2 × 2 ? Glans Ta None Intra-aortic
infusion
with
metho-
trexate
none 104/yes None None ?
12(37) 70 ? ? Verrucous Shaft, base
of penis T1 Mohs sur-
gery and
FTSG
Cisplatin
and fluo-
rouracil
with radio-
therapy
none 36/yes 16 None negative 2009
after recur-
rence
(local
excision)
13(35) 47 3 4 × 3 ? Prepuce,
glans Ta Total penec-
tomy Intra-aortic
infusion
with
metho-
trexate
Bilateral 37/no 18/partial Moderately
differ-
entiated
squamous
cell
? 2010
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Joetal. BMC Urol (2021) 21:13
Table 1 (continued)
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
due to
partial
response
Response Carcinoma,
malignant
transfor-
mation?
14(35) 28 72 5 × 4.5x2 Verrucous Prepuce,
glans Ta None Intra-aortic
infusion
with
metho-
trexate
None 45/yes None None ?
15(32) 42 ? 1 Warty Glans Ta Mohs sur-
gery None
(healed by
secondary
intention)
None 12/yes None Lichen
sclerosus ? 1987
16(31) 74 12 2 × 1.5 Warty Glans Ta Local exci-
sion Failed cryo-
therapy
with liquid
nitrogen
None 48/yes None Pseudoepi-
thelioma-
tous
negative 2000
Nodule (surgical
margin
2 cm)
Keratotic
and
micaceous
balanitis
17(23) 60 7 3 × 3 Verrucous,
ulcerative Prepuce,
glans Ta Partial
penec-
tomy
None None 24/yes None Human
immuno-
deficiency
virus infec-
tion
negative 2015
18(20) 71 6 2.8 × 1.6 Keratotic
hornlike Glans T1a Partial
penec-
tomy
None None 10/yes None None Negative 1990
total penec-
tomy (due to
residual
tumor
on the
resection
margins)
19(11) 61 ? 7 × 4 Cauliflower-
like Shaft T1a Local exc-
sion, skin
graft
None None 36/yes None None ? 2019
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Joetal. BMC Urol (2021) 21:13
Table 1 (continued)
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
20(10) 30 to 86 at least 12 1 to 8 Warty or
fungating 11 glans 10 Ta 9 partial
penec-
tomy
All none but All 72 to 228 All All none All 1985
mean 47 in 10 cases mean 3.6 (multiple
nodules 2 prepuce 3 T1 3 total
penec-
tomy
1 radio-
therapy none /yes none ?
(in 5 cases in 7 cases) 1 circumci-
sion (before total
penaec-
tomy)
13 cases 2,2,4,8,17 years)
in 3 cases
32(10) (1,2,4 months)
33(7) 40 to 63 8 to 25 2.5 to 6.2 Cauliflower-
like Glans Ta Glansec-
tomy None None 18 to 65 None None ? 2001
mean 54 ± 7 with frozen
section mean
38 ± 14
34(7) Cauliflower-
like Glans Ta Glansec-
tomy None None /Yes None None ?
35(7) Cauliflower-
like Glans Ta Partial
penec-
tomy after
None None 3 None ?
glansectomy
36(7) Cauliflower-
like Glans Ta Glansec-
tomy None None None None ?
37(6) 73 12 3 Verrucous coronary sul-
cus, shaft Ta Local exci-
sion None None 24/yes None None Negative 2017
38(5) 52 96 6 All coronoid
sulcus all Partial
penec-
tomy
All none All 6 to 60 All Squamous
atypical
hyperpla-
sia
All 2011
39(5) 85 48 3 Exophytic
papillary Glans Ta Local exci-
sion None mean 36 None None ?
40(5) 55 24 5 Cauliflower-
like Coronoid
sulcus Partial
penec-
tomy
/yes None
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Joetal. BMC Urol (2021) 21:13
Table 1 (continued)
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
41(5) 64 3 2 Glans Partial
penec-
tomy
None
42(5) 74 3 3 Glans Local exci-
sion Squamous
papilloma
43(5) 56 12 2 Glans Local exc-
sion Squamous
atypical
hyperpla-
sia
44(5) 52 3 2.5 Coronoid
sulcus Partial
penec-
tomy
None
45(5) 55 24 10 Shaft Partial
penec-
tomy
Squamous
atypical
hyperpla-
sia
46(5) 68 60 2 Coronoid
sulcus Circumci-
sion, Surgical
margin
2 cm for
partial
penec-
tomy
None
Partial
penec-
tomy
0.5–1 cm
for local
excision
47(5) 70 6 4.5 Glans Partial
penec-
tomy
Acknowl-
edging
excessive
resection
in 3 cases
None
48(5) 49 3 3 Glans Partial
penec-
tomy
For the
small-sized
mass
limited to
glans
None
49(4) 35 to 72 All ? 0.8 to 4 All 5 prepuce All All All none All 8 to 108 All All All 2015
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Joetal. BMC Urol (2021) 21:13
Table 1 (continued)
Case
(Ref.) Age
(years) Case history
(months) Tumor size
(Cm) Tumor
shape Tumor
location Stage
(TNM) Operation Adjuvant
threatment Lymphnode
metasatsis Follow up
(months)
/disease
free
Recurrence
(months
after)
Associated
disease HPV Year
of
issue
50(4) mean 51.5 Cauliflower-
like 1 prepuce,
coronoid
sulcus
Ta Partial
penec-
tomy
None /Yes but 1 case but 1
squamous
metapla-
sia with
?
51(4) 1 glans,
coronoid
sulcus
36, 60, 84 partial
hyperkera-
tosis
52(4) 3 glans
53(4)
54(4) 10 cases
55(4)
56(4)
57(4) 8 Biopsy
before
surgical
treatment
58(4) 2 circum-
cision
before
surgical
treatment
?; missing individual data, Ref.; reference number
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Joetal. BMC Urol (2021) 21:13
According to the regression analysis of age, case his-
tory, tumor size, tumor shape, tumor location, tumor
stage, adjuvant treatment, tumor recurrence, and treat-
ment trends over time did not appear to have a signifi-
cant negative or positive effect (data not shown).
In summary, the associations between tumor location
and treatment method and tumor depth and treatment
method were not statistically significant. Adjuvant ther-
apy tended to be performed alone or with local excision
preventing a penectomy or glansectomy. Partial penec-
tomy cases (aggressive treatment group) were predomi-
nantly reported in the 2010s. No intergroup differences
were seen in clinical results. erefore, our hypothesis
that aggressive treatment is more effective was rejected.
Discussion
Some studies have reported that PVC is observed in
approximately 2.4–24% of all penile cancers and 20% of
verruciform lesions of the penis; PVC is also observed
in patients with Buschke–Löwenstein, warty carci-
noma, and papillary SCC [1–3]. Several cases have been
reported during the past 2–3 decades among many coun-
tries due to its rarity [10, 48–51]. PVC primarily occurs
in the glans penis, and phimosis and redundant prepuce
are 2 of its important causes [2, 52]. Lichen sclerosus and
pseudoepitheliomatous, keratotic, and micaceous balani-
tis are other possible causes [31–33, 53]. Local squamous
epithelial hyperplasia and hyperkeratosis may be impor-
tant in the development of PVC [54, 55]. Clinically, they
do not cause significant pain, but they grow slowly and
uninhibited, sometimes invading the shaft over the glans.
In most cases, the patients present with a slow-growing
mass with multiple papillary lesions [4–6].
Biopsy and HPV PCR tests are basic diagnostic tools
for differentiating PVC from HPV-related tumors.
Increased immunohistochemical expression of markers
such as Mdm2 and Ki67 and low expression of Bcl-2 may
be useful for the detection of PVC [56–58]. Microscopi-
cally, the hematoxylin- and eosin-stained sections shows
extension of the epithelium downward into the underly-
ing tissues in a bulbous or drumstick process, while the
tumor exhibits clear boundaries and rich lymphocytic
infiltration into the surrounding mesenchyme [4–6].
To avoid misdiagnosis, repeated deeper biopsies are
recommended that include the basement membrane of
the papillomatous tumor, especially in cases in which
PVC is highly suspected. However, because the gross
morphology of PVC is very similar to that of condyloma
acuminatum, it can be difficult to identify. HPV is known
to be closely associated with penile cancer and condy-
loma acuminatum in most cases [8]. In contrast, in all
PVC cases, the pathogenesis is not associated with HPV
infection [3, 59–61]. us, an HPV-negative status may
be the key in the differential diagnosis of PVC. In our
study, the differential diagnosis from condyloma acumi-
natum was confirmed in only 8 cases. We assume that
diagnostic biopsy played a decisive role since HPV infec-
tion status was unknown.
Table 2 Cumulative data of clinical presentations
andtreatments
Total cases 58
Age (years) 28–86
Case History (months) 1–204
Size (Cm) 0.8–10
Tumor shape
Papillary cauliflower
Keratotic hornlike
Warty verrucous
Unknown
30
3
21
4
Location (cases)
Glans
Coronoid sulcus
Shaft
Prepuce
Prepuce and glans
Glans and coronoid sulcus and shaft
Prepuce and coronoid sulcus
Glans and coronoid sulcus
Coronoid sulcus and shaft
Coronoid sulcus involvement
33
4
4
7
4
1
2
2
1
10
Stage (cases)
Ta
T1 52
6
Treatment (cases)
No surgery
Local excision
Shaving
Mohs surgery
Circumcision
Glansectomy
Partial penectomy
Total penectomy
4
10
3
2
1
3
29
6
Adjuvant treatment (cases)
Radiotherapy
Chemotherapy
Chemoradiotherapy
Local therapy (CO2 laser, cryotherapy, intralesional interferon,
and topical fluorouracil)
1
6
2
6
Lymphnode metastasis (cases) 1
Follow up period (months) 6–228
Recurrence (cases) 7
Disease free (cases) 56
Surgical margin (Cm) 0.3–2
Cases following the year of issue (cases)
1970s
1980s
1990s
2000s
2010s
1
14
2
15
26
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Page 11 of 14
Joetal. BMC Urol (2021) 21:13
Surgical treatments reported in other studies focused
on aggressive treatments, including glansectomy and
partial or total penectomy with a 4–20-mm surgical mar-
gin [4, 5, 7, 8]. Partial penectomy with a 2-cm margin has
traditionally been the suggested treatment for tumors
involving the glans penis, with total penectomy being
indicated when the tumor involves a larger portion of the
penile shaft [49].
However, since PVC has a relatively rare incidence and
is termed carcinoma despite its favorable behavior, sur-
geons often lack of experience treating such cases and
decide to unnecessarily remove part or all of the penis.
Moreover, wide excision was commonly performed for
relatively small masses (≤ 3 cm) [5]. However, since the
1980s, local excision has been advised to preserve the
penis [4–6],15,17. Mohs surgery was adopted in cases of
PVC showing favorable behavior [15, 62]. e authors
agree that local excision should be the first choice of
treatment because of the favorable biological behavior
of PVC. Treatments have been suggested according to 2
general concepts: penectomy is mandatory because PVC
is malignant; and less aggressive treatment as local exci-
sion is sufficient because the biological behavior of PVC
resembles that of a benign tumor.
Table 3 Cross analysis (chi-square) withFisher’s exact test
*p < 0.05, **p < 0.01
Operation Total χ2
(p)
Less aggressive
treatment Aggressive
treatment
Tumor location Glans Case 11 22 33 2.532
(.686)
% 55.0% 57.9% 56.9%
Coronoid
sulcus involvement Case 4 6 10
% 20.0% 15.8% 17.2%
Stage Ta Case 17 35 52 .713
(.405)
% 85.0% 92.1% 89.7%
T1 Case 3 3 6
% 15.0% 7.9% 10.3%
Adjuvant treatment none Case 8 35 43 21.926**
(.000)
% 40.0% 92.1% 74.1%
Radiotherapy Case 0 1 1
% 0.0% 2.6% 1.7%
Chemotherapy Case 4 2 6
% 20.0% 5.3% 10.3%
Chemoradiotherapy Case 2 0 2
% 10.0% 0.0% 3.4%
Local therapy Case 6 0 6
% 30.0% 0.0% 10.3%
Recurrence No Case 17 34 51 .247
(.619)
% 85.0% 89.5% 87.9%
Yes Case 3 4 7
% 15.0% 10.5% 12.1%
Treatment trends over time fol-
lowing the year of issue 1970s Case 1 0 1 12.549**
(.005)
% 5.0% 0.0% 1.7%
1980s Case 2 12 14
% 10.0% 31.6% 24.1%
1990s Case 1 1 2
% 5.0% 2.6% 3.4%
2000s Case 10 5 15
% 50.0% 13.2% 25.9%
2010s Case 6 20 26
% 30.0% 52.6% 44.8%
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 12 of 14
Joetal. BMC Urol (2021) 21:13
is review revealed that the glans was the area most
often involved in cases of PVC. We expected that distal
and local lesions would be treated less aggressively. How-
ever, as a result, tumor location did not affect treatment
aggressiveness. Interestingly, the coronoid sulcus involve-
ment suggests that, in the absence of a dartos layer, penile
carcinoma would more rapidly infiltrate the penile fascia,
a known low-resistance pathway for local spread; thus,
clinicians would expect a higher risk of tumor recurrence
and inguinal involvement as well as a worse outcome.
us, we expected that coronoid sulcus involvement
would require more aggressive treatment. However, our
results demonstrated 11 cases in the less aggressive treat-
ment group versus 22 cases in the aggressive treatment
group, respectively. Although there were more cases in
the latter than the former group, the intergroup differ-
ence was insignificant.
Regarding tumor depth, PVC is defined as a superfi-
cial stage Ta lesion by the 2016 Tumor Node Metastasis
(TNM) classification, a so-called non-invasive verrucous
carcinoma. Although no statistically significant inter-
group difference was noted, aggressive treatments were
more often applied than less aggressive treatments for
superficial lesions. However, 20 cases of the less aggres-
sive treatment group showed good clinical results. Stage
T1 tumors were seen, even in cases of deeper lesions.
is means that less aggressive treatments with care-
ful follow-up of stage T1 tumors can also result in good
post-treatment results.
Even if a case of PVC is malignant, it may present as a
benign tumor. us, to preserve functional and cosmetic
results, we recommend that local excision with minimal
surgical margins followed by careful observation be the
first-line choice of treatment, especially for tumors meas-
uring < 3 cm and classified as stage T1. In other condi-
tions, the tumor should be considered not PVC and the
excision should be widened. In our study, we excluded
tumor staging beyond T2. Stage T2 penile cancers are
different from PVC and defined as invasive cancers such
as squamous cell carcinoma and others with bad progno-
sis. In these cases, aggressive treatment is recommended.
Regarding adjuvant therapy, preventive inguinal lym-
phadenectomy was hardly used because of rarity of evi-
dent lesions [4, 5, 9, 34, 35, 63, 64]. Conservative systemic
chemotherapy without surgery was reported [35, 38].
Other adjuvant therapies for the verrucous lesion have
been introduced, such as topical aminolevulinic acid–
photodynamic therapy; topical, systemic, or intralesional
interferon; cryotherapy; laser therapy; and radiation
[35–45, 65, 66]. Our results demonstrated that adjuvant
treatments were more predominantly applied when less
aggressive treatment was administered. is finding sup-
ports that conservative surgery could be the first choice
of treatment. However, the 4 cases treated with intral-
esional interferon and 1 case of cryotherapy with good
clinical results could not be evaluated due to the absence
of information on tumor stage [25, 41, 42].
is literature review revealed that inguinal lymphad-
enectomy was performed in certain patients; however,
no evident lesions were found in such cases [4, 5, 9, 34,
35, 63, 64]. e 1 case of lymph node metastasis reported
was suspected to be a combined lesion with moderately
differentiated SCC [35]. us, we agree that inguinal
lymphadenectomy is not an appropriate prophylactic
treatment. For lymphadenopathy, treatment with anti-
inflammatory drugs may be the treatment of choice, fol-
lowed by a lymph node biopsy as needed. us, if a case
of PVC is confirmed by biopsy and no signs of inguinal
lymphadenopathy are seen on physical examination, fur-
ther workups such as computed tomography or ultra-
sonography could be postponed initially, and high-end
MRI saved for later and then used if needed to investigate
tumor depth [67].
As for tumor behavior, complicated microlesions of
invasive SCC, a certain number of which eventually
progressed to other invasive types, have been observed
in < 30% of the reported cases of PVC [46, 68]. ere was
one case of recurrent SCC after anaplastic transforma-
tion following radiation therapy [47]. erefore, close fol-
low-up for the early detection of any sign of recurrence
requiring additional resection is essential after a less
aggressive treatment, such as local excision. In our study,
all but 2 cases achieved tumor-free status during long
follow-up periods despite 7 cases of recurrence. Regard-
ing those 2 cases, 1 was suspected as malignant trans-
formation after radiotherapy to anaplastic spindle cell
carcinoma [47] and the other was the previously men-
tioned lymph node metastasis case that eventually failed
treatment and required total penectomy due to partial
response after chemotherapy [35].
Despite the favorable clinical behavior of PVC and the
many studies emphasizing less aggressive treatments, the
use of aggressive treatment was predominantly reported
in the 2010s. However, we do not think that this reflects
the recent treatment trends because the timing of the
reported treatment does not represent the actual clinical
practice at the time.
However, information is still lacking about the associa-
tion between treatment and tumor condition, evidence of
which could lead us to define an appropriate guideline. Due
to the limitations of a literature review, controllable fac-
tors were often undetermined. us, we recommend that
future studies always include a unified scale for multiple
factors including tumor condition and functional outcome.
is mission will require long discussions and consensus of
many experts. Despite this limitation, we believe that our
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 13 of 14
Joetal. BMC Urol (2021) 21:13
findings are meaningful since this is the first review of diag-
nostic and treatment trends of PVC, a rare condition.
Conclusion
e review performed here revealed that PVC tends not
to recur or metastasize after resection but that surgical
treatment tends to remove too much tissue. However, in
most cases of local excision, the wound heals well and local
recurrence rarely occurs. erefore, considering the abil-
ity of local excision with minimal surgical margins to spare
the functional and cosmetic aspects of the penile shaft and
glans penis, we recommend it as the first-line choice of
treatment with observation, especially for tumors measur-
ing < 3cm and classified as stage T1 according to the 2016
tumor node metastasis clinical and pathological classifica-
tion for penile cancer.
Abbreviations
HPV: Human papilloma virus; MRI: Magnetic resonance imaging; PCR: Poly-
merase chain reaction; PVC: Penile verruca carcinoma; SCC: Squamous cell
carcinoma; TNM: Tumor node metastasis.
Acknowledgements
We would like to thank Editage (www.edita ge.co.kr) for English language
editing.
Authors’ contributions
HK have made substantial contributions to the conception of the work; SH, SK,
HYK and HC have made substantial contributions to the acquisition and analy-
sis of data; DJ have made substantial contributions to the design of the work
and the interpretation of data and have drafted the work and substantively
revised it. All authors have read and approved the final manuscript.
Funding
None.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent to publish
Not applicable.
Competing interests
The authors declare no conflicts of interest.
Author details
1 Department of Plastic and Reconstructive Surgery, Konkuk University School
of Medicine, Chungju, Republic of Korea. 2 Department of Anesthesiology
and Pain Medicine, Konkuk University School of Medicine, Chungju, Republic
of Korea. 3 Department of Urology, Konkuk University School of Medicine,
Gukwon-daero 82, 27376 Chungju, Chungbuk, Republic of Korea.
Received: 3 January 2020 Accepted: 21 December 2020
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