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International Journal of Colorectal Disease

https://doi.org/10.1007/s00384-020-03640-9

ORIGINAL ARTICLE

Management of anal intraepithelial neoplasia and anal squamous


cell carcinoma at a tertiary referral centre with a dedicated infectious
diseases unit: an 18-year review
M. Power Foley 1,2 & M. E. Kelly 1,2 & C Kerr 2,3 & C. Kennedy 1,2 & D. Gallagher 2,4 & C. Gillham 2,5 & B. J. Mehigan 1,2 &
P. H. McCormick 1,2 & C. Bergin 2,3 & J. O. Larkin 1,2

Accepted: 14 May 2020


# Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract
Introduction Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human
immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is
an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that
HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes.
Methods Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a
dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and
outcomes between HMSH and non-HMSH patients.
Results One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%).
Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26–88). Thirty-six percent of all patients
attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM).
Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy.
Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage
APR. Overall 3-year survival (3YS) was 76%.
HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM.
HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall
outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037).
Conclusion ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger,
high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies
and earlier intervention.

Keywords Anal Pathology Squamous Cell Carcinoma . Anal Intraepithelial Neoplasia . HIV Medicine/Sexual Health

What does this paper add to the literature?


The high incidence of premalignant and malignant anal pathology among
HIV-Medicine/Sexual Health service users is well documented in the
literature; however, to date, there are no studies looking at oncological
outcomes in this unique cohort from a colorectal surgery perspective.

* M. Power Foley 3
Department of Genitourinary Medicine and Infectious Disease, St
foleymp@tcd.ie James’ Hospital, Dublin 8, Ireland
4
Department of Medical Oncology, St James’ Hospital, Dublin 8,
1
Department of Colorectal & General Surgery, St James’ Hospital, Ireland
Dublin 8, Ireland 5
Department of Radiation Oncology, St James’ Hospital, Dublin 8,
2
School of Medicine, Trinity College Dublin, Dublin 2, Ireland Ireland
Int J Colorectal Dis

Introduction Methods

Anal squamous cell carcinoma (ASCC) accounts for 4% Study design and participants
of all lower gastrointestinal tract cancers [1]. The combi-
nation of increasing incidence rates and an observed epi- This single-centre series, examining the period from 2000
demiological shift from older, female patients to younger, to 2020, was conducted in accordance with the
male patients engaging in high-risk sexual activity has “Strengthening the reporting of observational studies in
renewed interest in this rare malignancy [2, 3]. In the epidemiology (STROBE) statement” [1]. Prior to com-
USA, a threefold increase in incidence in men (from 1 mencement, ethical approval for a retrospective review
to 3 per 100,000) and a 1.7-fold increase in women (from was granted by the local institutional committee. All pa-
1.4. to 2.4 per 100,000) have been observed between tients treated for biopsy-proven anal intraepithelial neo-
1973 and 2009. The most recent Surveillance plasia and anal squamous cell carcinoma between 2000
Epidemiology and End Results (SEER) statistics report and 2019 at our institution were included in the analysis.
the median age of diagnosis is 62 years, and that the Patients were identified from a prospectively maintained
overall incidence remains slightly higher in women. The local cancer database (ASCC) and an electronic histopa-
5-year survival rate is reported to be 63.8% for all disease thology database (AIN). Further demographic, clinical,
stages [4]. The National Cancer Registry of Ireland histopathological and outcome data were extracted from
(NCRI) review of HPV-related cancers reports a signifi- electronic patient records. Demographic data included
cant annual increase (3–4%) in ASCC over the last decade age, comorbidities, risk factors and attendance at our in-
[5]. Cigarette smoking, chronic immunosuppression (hu- stitution’s HIV Medicine/Sexual Health clinic.
man immunodeficiency virus (HIV) infections, solid-
organ transplant recipients on anti-rejection regimens or
patients on long-term corticosteroids) and high-risk sexual Aims
activity (defined by the World Health Organisation as
engaging in unprotected sexual intercourse, penetrative Primary aims were identifying the prevalence of known risk
anal intercourse, and sexual intercourse with multiple factors for anal pathology among the total cohort and the HIV
partners, intravenous drug users, sex workers or partners Medicine/Sexual Health subcohort, and investigating the im-
with prior sexually transmitted infections) are all pact of HIV Medicine/Sexual Health involvement on the age
established risk factors for ASCC [6–9]. However, chron- of ASCC diagnosis, stage at diagnosis and objective survival
ic infection with the oncogenic human papillomavirus outcomes. Secondary aims were reviewing overall manage-
(HPV) is the dominant driver of carcinogenesis in ment of ASCC at our institution.
ASCC and its precursor lesion, anal intraepithelial neopla-
sia [10, 11]. It has been determined that 88–94% of ASCC
can be attributed to HPV, particularly high-risk genotypes Analysis
like HPV-16 and HPV-18 [12–15].
Multiple international studies have reported significantly All data were tabulated using Microsoft Excel 2020
higher rates of ASCC in HIV-positive patients, compared with (Microsoft Corporation, Redmond, WA, USA) and
the general public [16–19]. Recently, the synergistic effect of Statistical Package for the Social Sciences (SPSS) soft-
immunosuppressive HIV infection with oncogenic HPV in- ware Version 24.0 (IBM SPSS Inc., Armonk, NY, USA.
fection has been identified as a strong risk factor for the de- IBM Corp) was used for data analysis. Normally distrib-
velopment of high-grade AIN and ASCC. Men-who-have- uted continuous data were expressed as mean ± standard
sex-with-men (MSM) are deemed to be a high-risk population deviation (SD), while median (range) was used to de-
[20, 21]. scribe the non-normally distributed continuous data.
There is a significant overlap between the patients at Categorical variables were presented as count and percent.
highest risk for AIN and ASCC and those attending HIV Chi-square and one-way ANOVA tests were used to as-
Medicine/Sexual Health (HMSH) services. The catchment ar- sess significance between categorical variables. Non-
ea of our institution has the highest prevalence of HIV in parametric data was assessed using a Mann-Whitney U
Ireland (2.25/1000) [22, 23]. As of 2018, 2532 HIV patients test or a Kruskall-Wallis test, depending on the number
attended the HMSH clinic at our institution, of whom 48% (n of variables involved in the analysis. Kaplan Meier
= 1217) were MSM [24]. We sought to investigate whether Survival curves and life table analysis were used to assess
patients attending the HIV medicine/sexual health services differences in overall and disease-specific survival be-
who developed AIN or ASCC presented to colorectal sur- tween the two subcohorts at 3 and 5 years. A p value of
geons at earlier stages and had better outcomes. < 0.05 was considered statistically significant.
Int J Colorectal Dis

Fig. 1 Graphical representation


of two yearly incidence of all anal
pathology, AIN, ASCC at our
institution between 2000 and
2018, demonstrating increasing
incidence trends in ASCC and
overall

Results pathology at a younger age, notably HIV-positive patients (p


< 0.001), HPV-positive patients (p = 0.030), HMSH service
Incidence, demographics and prevalence of risk users (p < 0.001) and MSM (p < 0.001).
factors Tables 3, 4, and 5 outlines the prevalence of various
established risk factors for anal pathology, including smoking
Over an 18-year period, 109 patients were treated for AIN or (69% of total cohort), HPV-positive status (45%) and HIV-
ASCC. Eighty-five patients (78%) had invasive squamous cell positive status (28.4%).
carcinoma of the anus (ASCC). Of these 85, twenty patients Forty-four (40.4%) of the total cohort had been treated for a
(18.3% of total cohort, 23% of ASCC cohort) had newly di- prior sexually transmitted infection (STI), including twelve
agnosed concurrent AIN at the time of ASCC diagnosis. A cases of syphilis and fourteen cases of genital herpes simplex
further 24 patients (22%) had AIN only, with no malignant virus (HSV). Seventeen out of thirty-nine women (43.5%) had
anal histology. prior gynaecological neoplasia. Three patients had a prior sol-
The annual incidence of ASCC at our institution increased id organ transplant and were on lifelong immunosuppression.
during the study period [Fig. 1].
Seventy patients (64.2%) of the total cohort were male,
Progression from AIN to ASCC
accounting for 59% of the ASCC cohort and 83.3% of the
AIN cohort [Table 1]. Nine male patients (18%) and twelve
Six patients (7%) progressed from AIN to ASCC during the
female patients (34.28%) had both AIN and SCC at initial
study period. The median interval between the diagnosis of
diagnosis. Seventy-one percent of the total male cohort had
AIN and ASCC in these six patients was 25.0 months (range
invasive histology, compared with 89.7% of the total female
1–108). No risk factors demonstrated significance in our co-
cohort.
hort (Fig. 2).
The median age at diagnosis in the total cohort was 51
.
years (range 25–88). We looked at the impact of various fac-
tors on the age of diagnosis using one-way ANOVA non-
parametrical tests, tabulated in Table 2. Patients with ASCC Management of anal squamous cell carcinoma
were diagnosed at an older age, compared to patients with
premalignant pathology (p = 0.004). It was consistently ob- Of note, specific treatment details were unavailable for two
served that high-risk patients were diagnosed with anal patients. Of those with complete data available, eighty-one
(97.5%) were managed with curative intent, while two
Table 1 Breakdown of gender in the total cohort, ASCC subcohort and proceeded directly to palliation. Table 6 outlines the manage-
AIN subcohort
ment strategies. Fifteen patients had a primary surgical resec-
Gender Male Female tion, with fourteen excision biopsies of locally resectable dis-
ease (not involving the sphincters). One patient had an exten-
Total cohort 64.2% 35.8% sive perineal resection of perianal necrotising fasciitis caused
n = 70 n = 39
by an undiagnosed ASCC. Sixty-seven patients (80.7%) had
ASCC 59% 41%
n = 50 n = 35
primary chemoradiation therapy, while a single patient had
AIN 83.3% n = 20 16.7%
radiation monotherapy. Of this cohort, seven patients did not
n=4 respond to medical therapy, of whom four ultimately required
a salvage APR, while the remaining three were palliated due
Table 2 Median age at diagnosis in the total cohort, ASCC subcohort and AIN subcohort. Breakdown of median age at diagnosis in each group in the presence/absence of various risk factors for anal
pathology, with statistical significant noted

Age [years (range)]

Total Gender HIV MSM (males) HMSH

Male Female HIV + ve HIV – ve Yes No Yes No

Total cohort 51 years 50.5 years 54.0 years 41.0 years 55.5 years 41.0 years 56.0 years 41.0 years 58.0 years
(25–88) (26–82) (25–88) (26–75) (25–88) (26–75) (32–82) (26–75) (25–88)
p = 0.112 *p < 0.001 *p < 0.001 *p < 0.001
ASCC 53.0 years 52.0 years (31–82) 54.0 years (25–88) 43.0 years 57.0 years 46.00 years 58.00 years 41 years 58 years
(25–88) (26–75) (25–88) (31–75) (32–82) (26–75) (25–88)
p = 0.701 *p < 0.001 *p = 0.009 *p < 0.001
AIN 42.0 years 41.0 years 61.0 years 36.0 years 49.0 years 33.50 years 50.0 years 38.50 years 56.50 years
(26–67) (26–67) (38–76) (26–58) (30–76) (26–67) (36–76) (26–67) (38–76)
p = 0.081 p = 0.055 *p = 0.025 *p = 0.009

Table 3 Breakdown of the presence/absence of well-established risk factors for anal pathology among the total cohort, ASCC subcohort and AIN subcohort

Risk factors

Smokers HIV HMSH MSM (males) HPV

Yes No Yes No Yes No Yes No Yes No

Total cohort 68.8% (n = 75) 31.2% 28.4% (n = 31) 71.6% 35.8% 64.2% 41.4% (n = 29) 58.6% 45% (n = 49) 55%
(n = 109) (n = 34) (n = 78) (n = 39) (n = 70) (n = 41) (n = 60)
ASCC 71.8% (n = 61) 28.2% 21% (n = 18) 79% 25% (n = 21) 75% 34% (n = 17) 66% 35% (n = 30) 65%
(n = 85) (n = 24) (n = 67) (n = 64) (n = 33) (n = 55)
AIN 58.3% (n = 14) 41.7% 54.2% 45.8% 75% (n = 18) 25% 60% (n = 12) 40% 79.2% (n = 19) 20.8%
(n = 24) (n = 10) (n = 13) (n = 21) (n = 6) (n = 8) (n = 5)
Int J Colorectal Dis
Int J Colorectal Dis

Table 4 Breakdown of the presence/absence of well-established risk factors among the total cohort, ASCC subcohort and AIN subcohort, with
demonstration of statistically significant higher prevalence in patients attending GUIDE services compared with those not known to GUIDE

HIV medicine/sexual health cohort Community referrals p

Total ASCC AIN Total ASCC AIN


n (%) 39 (36%) 21 (24%) 18 (75%) 70 (64%) 64 (76%) 6 (25%)

Male gender n = 36, 92% n = 18, 86% n = 18, 100% n = 34, 48.5% n = 32, 50% n = 2, 33% * < 0.001
Age 41.0 years 41.0 years 38.5 years 57.5 years 57.5 years 56.5 years * < 0.001
HIV + ve n = 30, 77% n = 17, 81% n = 13, 72% n = 1, 1.5% n = 1, 2% 0 * < 0.001
HPV + ve n = 31, 82% n = 15, 75% n = 16, 89% n = 18, 27% n = 15, 25% n = 3, 50% * < 0.001
MSM n = 26, 72% n = 14, 78% n = 12, 66% n = 3, 9% n = 3, 9% 0 * < 0.001
STI n = 35, 92% n = 18, 86% n = 17, 94% n = 9, 14% n = 7, 12% n = 2, 33% * < 0.001
Smoker n = 25, 66% n = 16, 80% n = 9, 50% n = 50, 76% n = 45, 75% n = 5, 83% 0.275

to the extent of disease and/or severe co-morbidities. Twelve [26–28]. However, there remains a paucity of literature
patients (14%) had biopsy-proven recurrence after primary looking specifically at the impact of early involvement on
treatment, ten after chemoradiation and two after primary sur- ASCC outcomes. It would seem reasonable that patients
gical resection. Two-thirds recurred locally (n = 8), while four who are compliant with attendance at regular HMSH appoint-
had distant metastases. Three patients were palliated at time of ments would be more vigilant about anorectal pathology and
recurrence. Overall, seven patients required a salvage APR, might therefore be referred at earlier stages to colorectal ser-
71% (n = 5) of whom had negative (R0) resection margins. vices. Our results observed that a 3-year overall survival was
The two patients with incomplete resections went on to devel- significantly higher in HMSH patients than non-HMSH at-
op further local recurrence within 8 and 9 months, respective- tendees (93% vs. to 72%, p = 0.037) and support the recom-
ly, at which stage they were palliated and later died due to mendation of a formalised surveillance pathway incorporating
complications of recurrent ASCC. both HMSH and colorectal clinical inputs. Although beyond
the scope of this review, the association between HPV infec-
Treatment and outcomes in cohort versus cohort tion and other genitourinary tract squamous cell carcinomas
highlights the importance of collaboration not only between
Table 6 describes the breakdown of disease characteristics, HMSH and colorectal surgeons, but also with gynaecologists.
management strategies and outcomes in total cohort, and il- Our institution has fostered a strong link between medical and
lustration of any significance differences between HMSH and surgical oncology, and gynaecology. All female patients with
non-HMSH cohorts a new diagnosis of AIN or ASCC are referred for full
HMSH patients had lower rates of recurrence, better sensi-
tivity to chemoradiation and less need for salvage APRs.
Table 7 illustrates the mortality and survival outcomes in Table 5 Breakdown of risk factors for progression from AIN to ASCC,
both cohorts. The overall mortality rate in the ASCC cohort with odds ratio (95% confidence intervals) and statistical significance of
was 30% (n = 25), with a cancer-specific mortality rate of 17% each
(n = 14). At 3 years, the HMSH cohort demonstrated a signif- Risk factors for progression AIN to ASCC
icantly better overall survival rate than non-HMSH patients (p
= 0.037). In addition, a 3-year overall survival for ASCC was Factor n (%) Odds ratio p value
also higher in HMSH cohort, as shown in Fig. 3.
Male gender 3 (50%) OR 1.469 p = 0.455
(95% CI 0.279–7.741)
Smoker 3 (50%) OR 3.625 p = 0.213
Discussion (95% CI 0.667–19.71)
HPV 4 (66.6%) OR 0.277 p = 0.335
(95% CI 0.047–1.614)
The incidence of anal pathology (AIN and ASCC) is increas- HIV 2 (33.3%) OR 0.542 p = 0.833
ing internationally. Our results are consistent with internation- (95% CI 0.091–3.232)
al reports, with an overall 5-year survival of 65% [25]. Over MSM 2 (66.6%) OR 0.268 p = 0.417
(95% CI 0.022–3.202)
one-third of our patients (36%) came from HIV Medicine/
HMSH 2 (33.3%) OR 0.679 p = 0.898
Sexual Health clinics, reaffirming studies which advocate (95% CI 0.115–4.005)
the development of dedicated screening and management
Int J Colorectal Dis

Fig. 2 Graphical representation Biennial incidence of Anal Pathology in HMSH and Total Cohorts
of two yearly incidence of all anal 25
pathology and anal pathology in
HMSH and non-HMSH cohorts
at our institution between 2000 20

Number of New Cases


and 2018, demonstrating increas-
ing incidence trends in ASCC and All Pathology
15
overall
HMSH
10
Non-HMSH

0
2000 2002 2004 2006 2008 2010 2012 2014 2016 2018
Year

gynaecological assessment prior to commencing treatment to established. In our cohort, 63 patients (76%) underwent primary
screen for concurrent HPV-related genital tract lesions. chemoradiation therapy. The only patients for whom primary
Conversely, 15% of our female cohort (n = 6) were referred surgical intervention is recommended are T1N0M0 patients with
by gynaecologists who had identified suspicious anal lesions small, well-differentiated lesions not involving the sphincter
[29]. muscles [41]. Seventeen (22%) of our ASCC cohort had T1
The treatment of anal cancer has changed significantly since lesions, of whom ten underwent primary surgical resection while
1974, when the introduction of the Nigro chemotherapy regimen, the remaining seven patients had chemoradiation.
using 5-FU and mitomycin C (MF), marked a paradigm shift in Osborne et al. observed that upwards of 30% of patients
management, from surgical to medical therapies [30]. In 1996, have persistent or recurrent disease after chemoradiotherapy
the seminal ACT1 randomised controlled trial (RCT) reported [42]. The main risk factors for this included the following:
this chemotherapy regimen combined with radiation therapy HIV infection, high T and/or N stage at diagnosis and/or in-
(MF-CRT) significantly reduced locoregional failure [31]. ability to complete chemoradiotherapy. In our cohort, fifteen
Since ACT1, successive RTCs have created a strong evidence patients (17.6%) had a recurrence and three patients (3.5%)
base supporting concurrent chemoradiation (MR-CRT) as the had persistent disease. Interestingly, in our series, neither HIV
gold standard primary treatment for ASCC [32–40]. The concept status (p = 0.615) nor lymph node status (p = 0.615) influ-
of organ preservation, while retaining APR as an option for enced recurrence. However, 66% (n = 10) of those with recur-
salvage of recurrence or persistent disease, is now well rent disease had a T stage of at least T3 at initial presentation.

Table 6 illustrates the


comparison of management Total HMSH Non-HMSH p value
strategies and outcomes in vs
patients. Patients tended to be n (%) 85 21 (25%) 64 (75%)
diagnosed at earlier stages with
smaller lesions more amenable to Age 53.0 years 41 years 57.5 years *p < 0.001
initial surgical management with T stage T1 17 (22%) 7 (35%) 10 (17%) p = 0.097
sphincter-sparing local resection
T2 23 (29%) 5 (25%) 18 (31%) p = 0.610
than did patients.
T3 24 (31%) 6 (30%) 18 (31%) p = 0.931
T4 14 (18%) 2 (10%) 12 (21%) p = 0.283
Nodal disease 22 (26%) 6 (28.5%) 16 (25.8%) p = 0.804
Distant metastasis 5 (6%) 1 (5%) 4 (6.5%) p = 0.767
Curative intent 80 (97%) 21 (100%) 59 (97%) p = 0.401
Primary surgical 15 (17.5%) 5 (24%) 10 (16%) p = 0.296
Primary chemo/RT 63 (76%) 16 (76%) 53 (84%) p = 0.411
Stoma 24 (28%) 5 (23%) 19 (33%) p = 0.641
No response to chemo/RT 9 (14%) 1 (6.25%) 8 (15%) p = 0.403
Recurrence 15 (17.6%) 3 (14%) 12 (31%) p = 0.380
APR 8 (9.5%) 2 6 p = 0.537
Negative margins 71.5% 100% 75% p = 0.180
Int J Colorectal Dis

0.676

0.533
Anal intraepithelial neoplasia (AIN) is a recognised precur-


sor to anal cancer, with HPV infection implicated in potenti-
Breakdown of disease characteristics, management strategies and outcomes in total cohort, and illustration of any significance differences between HMSH and non-HMSH cohorts
ating the neoplastic process. The natural history of the disease

(n = 3)

93.3%
parallels that of cervical intraepithelial neoplasia (CIN) and

Total

14%
24
cervical cancer [14, 15]. Low-grade lesions can be managed


with surveillance only, whereas options for high-grade lesions
include topical treatments (imiquimod, 5-fluoro uracil acid (5-
FU) or trichloroacetic acid), ablation (electrocautery (ECA),
HMSH

(n = 1)

100%
infrared coagulation (IRC) or laser) or traditional surgical ex-
Non-

20%
6 cision [43]. Lesions persisting despite topical treatment should


be excised and patients entered into a structured surveillance
programme [44]. However, the risk and natural progression
HMSH

(n = 2)
12.5%

90.9%
from premalignant AIN to invasive cancer remains unclear.
18


High-risk HPV strains, MSM, HIV, solid-organ transplant
recipients and previous HPV-related dysplasia and/or neopla-
0.466

0.715

0.050
AIN

sia at other sites have all previously been shown to be risk


p

factors for progression [45, 46]. In our cohort, the overall


progression rate from AIN to ASCC was 7% (n = 6 of 85),
(n = 25)

(n = 14)

all of whom had high-grade AIN III.


76.2%
Total

30%

17%

To date, there has been no clear international consensus


85

regarding the optimal frequency of screening high-risk


groups. The majority of calls for focused screening programs
come from HMSH services. Some have advocated screening
(n = 20)

(n = 11)
32.35%
HMSH

for MSM and/or HIV patients, based on the rates of anal


17.7%

69.7%
Non-

pathology observed in their attendance cohort. Goldie et al.


64
ASCC cohort

reported that screening for AIN in HIV-positive MSM patients


is cost effective [47]. However, routine screening programs
93.75%
HMSH

(n = 5)

(n = 3)
23.8%

14.2%

remain contentious. Despite this, there is robust support for


21

prophylactic vaccination against HPV in high-risk patients


[48, 49]. In addition, many advocates for joint HMSH and
colorectal out-patient clinics to expedite prompt investigation
*0.037
0.171

0.274

and management of suspicious lesions. It is evident from this


p

study that patients made up a significant portion of our total


(n = 28)

(n = 14)
26.9%

13.7%

79.7%
Total

109

(n = 21)

(n = 11)
HMSH

31.3%

72.3%
Non-

16%
70
Total cohort

HMSH

(n = 7)

(n = 3)
20.5%

92.6%
8.5%
39

Disease-specific mortality
Overall mortality
Mortality

Fig. 3 Kaplan-Meyer Curve illustrating 3-year survival in the ASCC


Table 7

cohort in HMSH and non-HMSH cohorts. The difference was not signif-
3YS

icant (p = 0.0504)
n
Int J Colorectal Dis

anal pathology cohort (36%, n = 39), and one-quarter of the Cancer Institute, DCCPS, Surveillance Research Program, released
April 2018, based on the November 2017 sub- mission. Anal
ASCC cohort (25%, n = 21). Our results support the imple-
Cancer, (1973-2009).
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and coloproctology services. This is supported by the fact that HPV-associated cancers. NCR, Cork, Ireland
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epidemiology of anal cancer. Surg Oncol Clin N Am 13:263–275
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7. Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA,
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lights the opportunity for early intervention and therefore may (2004) Human papillomavirus, smoking, and sexual practices in the
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Acknowledgements We would like to acknowledge Ms Chris Gleeson, Variants of squamous cell car- cinoma of the anal canal and perianal
the data manager of the colorectal oncology service at our institution. We skin and their relation to human pap- illomaviruses. Cancer Res 59:
also acknowledge the work done by Ms Lara Gander and Ms Caoimhe 753–757
Ryan, two medical students from Trinity College Dublin. 12. Yhim H-Y, Lee N-R, Song E-K, Kwak J-Y, Lee ST, Kim JH, Kim
JS, Park HS, Chung IJ, Shim HJ, Hwang JE, Kim HR, Nam TK,
Availability of data and material Not applicable. Park MR, Shim H, Park HS, Kim HS, Yim CY (2011) The prog-
Code availability SPSS version 24.0 was used for statistical analysis, no nostic significance of tumor human papillomavirus status for pa-
customised codes were generated. tients with anal squamous cell carcinoma treated with combined
chemoradiotherapy. Int J Cancer 129:1752–1760. https://doi.org/
Compliance with ethical standards 10.1002/ijc.25825
13. Ouhoummane N, Steben M, Coutlée F, Vuong T, Forest P, Rodier
C, Louchini R, Duarte E, Brassard P (2013) Squamous anal cancer:
Ethical approval Approval was granted by the institution’s ethics com- patient characteristics and HPV type distribution. Cancer Epidemiol
mittee prior to receiving access to the local cancer database. 37:807–812. https://doi.org/10.1016/j.canep.2013.09.015
14. Shah KV (1997) Human papillomaviruses and anogenital cancers.
Conflict of interest The authors declare that they have no conflict of N Engl J Med 337:1386–1388. https://doi.org/10.1056/
interest. NEJM199711063371911
15. Abramowitz L, Jacquard AC, Jaroud F, Haesebaert J, Siproudhis L,
Pradat P, Aynaud O, Leocmach Y, Soubeyrand B, Dachez R,
Riethmuller D, Mougin C, Pretet JL, Denis F (2011) Human pap-
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