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19 Sexually Transmitted Infections
Fig. 19.11 Perianal condyloma due to HPV infection
• Patients with warts within the anal canal may
have a history of receptive anal intercourse,
but not necessarily.
• Symptoms may include pain, pruritus, discomfort, or bleeding, depending on the location and size of the warts.
• Patients with HIV infection or another source
of immunosuppression are more likely to
develop genital warts, and these warts are less
likely to respond to treatment and more likely
to recur.
• The high-risk HPV types can cause invasive
squamous cell cancers of the anus.
– Squamous cell carcinoma occurs more fre-
quently in patients who are immunosuppressed, especially in patients who are
coinfected with HIV.
– Disturbances in the peripheral immune
function in the anal mucosa may explain
this increased risk to progress to invasive
anal cancer.
Testing
• HPV testing can be used to screen women for
cervical cancer, but screening for HPV is not
indicated for men, sex partners of women with
known HPV, adolescent women, or for other
HPV-related malignancies such as anal
cancer.
• As certain high-risk populations such as HIVpositive MSM have seen a rise in incidence of
invasive anal squamous cell carcinoma,
screening programs to detect precursor lesions
273
have been developed to prevent progression to
invasive cancer.
• Liquid-based anorectal cytology specimens
are the preferred specimen type to screen for
high-grade anal dysplasia.
• Self-collected samples are less sensitive than
clinician-collected samples.
• Patient with positive ndings should be
referred to a specialist for high-resolution
anoscopy or routine anoscopy and
monitoring.
Treatment
• The indication to treat anogenital warts is to
relieve symptoms.
• Untreated genital warts may self-resolve or
worsen.
• Treatment does not affect the risk of transmission of HPV.
• External genital warts can be treated in a variety of ways (Table19.3).
– Patients may apply their own treatment at
home using podolox solution or gel,
imiquimod cream, or sinecatechins
ointment.
– Provider-administered options include
cryotherapy, podophyllin resin, or trichloroacetic or bichloroacetic acid.
– Patients with extensive genital warts may
warrant surgical management.
• Anal condyloma– including warts in the anal
canal and the distal rectum – can be treated
with cryotherapy, TCA or BCA, or surgical
therapy.
• High-resolution anoscopy may be indicated to
inspect for high-grade dysplasia as well.
• The management of high-grade anal dysplasia, the precursor to invasive squamous cell
carcinoma, remains a controversial topic.
• While some clinicians view ablation or
destruction of high-grade dysplasia as an
important strategy to prevent progression to
invasive cancer, others disagree with this
approach.
• Patients with high-grade intra-anal dysplasia
who undergo ablation have recurrence rates of
about 50% overall (higher in HIV-positive
patients) but a low risk of developing anal
cancer.
274
C. J. Kin and M. L. Welton
Vaccine
• The two HPV vaccines available are the bivalent vaccine, which protects against high-risk
oncogenic HPV types 16 and 18, and the
quadrivalent vaccine which protects against
HPV types 6, 11, 16, and 18 and should be
given before one become sexually active.
• Both are approved for girls and boys aged
9–26years old.
• The quadrivalent vaccine has been shown to
reduce the rates of high-grade anal dysplasia
among MSM and may help to reduce the risk
of anal cancer.
HIV andAIDS
Epidemiology
• Over 1million people in the USA have HIV,
and over half of those infected are MSM.
• A quarter of those patients reported high-risk
sexual practices such as unprotected sexual
intercourse with a casual partner or sex in
exchange for money or drugs, and almost half
of those patients reported using noninjection
drugs over the past year.
Testing
• HIV screening is recommended for all patients
who present for STI testing.
• Positive screening tests for HIV antibody
require conrmatory testing before a diagnosis can be made.
• If patient is suspected of having acute HIV
infection, then a nucleic acid test should be
performed in addition to the antibody test, and
the patient should be referred immediately to
an infectious disease specialist.
• The FDA has recently approved combination
tests detecting both HIV antigen and antibody,
as well as tests that differentiate HIV-1 from
HIV-2.
– Fissures in HIV-positive patients may be a
manifestation of HIV but could also represent coinfection with other STIs such as
HSV or syphilis.
– Treatment of ssures in patients with HIV
should consist of the same treatment undertaken for ssures in the general
population.
• Anal ulcers are another source of anal pain in
patients with HIV and are located in a more
proximal location within the anal canal– often
above the dentate line– and are broader and
more ulcerative than ssures.
• Perianal abscesses and stulas are common in
patients with HIV or AIDS.
– Patients with well-controlled HIV and nor-
mal CD4 counts who develop abscesses
and stulas can be treated with the same
surgical techniques as one would do for
patients without HIV.
– However, abscesses in patients with AIDS
should be treated with smaller incisions,
favoring drain placement over larger
incisions.
– Fistulas in patients with advanced or poorly
controlled AIDS should be treated with
placement of draining setons rather than
stulotomy to avoid the creation of a nonhealing wound.
• External thrombosed hemorrhoids and symptomatic internal hemorrhoids in patients with
HIV or AIDS should be treated in the same
manner as those occurring in patients without
HIV.
• Hemorrhoidectomy is safe in HIV-positive
patients without AIDS; patients with advanced
or poorly controlled AIDS and severe hemorrhoids not amenable to banding may have
wound healing problems.
Molluscum Contagiosum
Anorectal Issues
• Anorectal complaints such as pain due to ssures may be the presenting symptom of
patients with HIV infection.
• Molluscum contagiosum is a common cutaneous viral infection caused by the molluscipox
virus, causing small, waxy, dome-shaped
umbilicated papules (Fig.19.12).
19 Sexually Transmitted Infections
Fig. 19.12 Molluscum contagiosum lesions present as
waxy dome-shaped umbilicated papules
275
• Curettage, excision, and cryotherapy are
the most common methods of
treatment.
• These treatments should not be performed in patients with immunosuppression due to the risk of nonhealing
wounds and superinfection with other
bacterial, viral, or fungal organisms.
• For these patients topical treatments such as
imiquimod 5% cream may be helpful without incurring the risk of open surgical
wounds.
Pubic Lice: Phthirus pubis
• It is second only to genital warts as the most
common non-ulcerative STI, affecting up to
5% of the population, 18% of patients with
immunosuppression, and 30% of patients with
advanced AIDS.
• Secondary bacterial infection may occur especially if patients tend to scratch the lesions.
• Mollusca contagiosa occur frequently in
young children, but their occurrence in adults
is usually considered an STI and involves the
pubic area.
– Risk factors include shaving.
– Transmission occurs through skin-to-skin
contact, and autoinoculation can also occur
to spread to other sites.
– Sexual contact can lead to transmission
from the genitalia to the oral mucosa, conjunctiva, and cornea.
• Diagnosis can be made by visual inspection
although if there is difculty, then dermatoscopy revealing orices, vessels, and specic
vascular patterns can help conrm the
diagnosis.
• A recent PCR test has been developed as well
for the molluscum contagiosum virus.
• Immunocompetent patients will self-resolve
these lesions over a period of months to years,
so most patients prefer treatment.
– Treatment consists of removal of the
lesions, similar to the treatment of genital
warts.
• Pubic lice are obligate blood-sucking parasites, and infestation is diagnosed by nding
lice on pubic hair (Fig.19.13).
• As lice can neither jump nor y, transmission
is due to close contact.
• Therefore, the diagnosis of pubic lice should
prompt testing for other STIs.
Fig. 19.13 Pubic lice infestation causes severe pruritus
and can be treated with permethrin 1% cream. (Photograph
courtesy of Stephen Goldstone, MD)
276
• The increased incidence of pubic hair removal
has been associated with a lower incidence of
pubic lice infections due to destruction of their
natural habitat.
• The CDC recommends permethrin 1% cream
or pyrethrins 0.3%/piperonyl botuxide 4%
cream as rst-line therapy for pubic lice.
• Alternative regimens include malathion 0.5%
lotion or oral ivermectin.
• Laundering clothes and bedding in hot water
should be done as well to prevent reinfection
and transmission.
Scabies
• Scabies is caused by the mite Sarcoptes scabiei var. hominis.
• Scabies transmission is via skin-to-skin contact, as the mites neither jump nor y.
• Scabies most commonly occurs in young children but can also occur in patients subject to
overcrowded conditions, poor hygiene, and
homelessness and via sexual contact.
• The mites burrow into the skin, creating wavy
scaly lines on the skin surface, usually located
on the hands and feets, typically in nger
webs.
• The infestation causes an intense pruritic rash
localized in a characteristic distribution in the
armpits, elbow creases, wrists, and groin areas
(Fig.19.14).
• Infants, children, and immunosuppressed
patients may develop a more severe vesicular
and pustular rash.
• Diagnosis can be made by visual inspection
and history.
• Skin scrapings of the burrows, papules, and
vesicles can be performed by applying min-
C. J. Kin and M. L. Welton
Fig. 19.14 Scabies infestation causing an intensely pruritic rash can be treated with permethrin 5% cream.
(Photograph courtesy of Stephen Goldstone, MD)
eral oil to the skin and scraping laterally across
the lesion with a scalpel and examining the
scraping microscopically for mites, eggs, and
fecal pellets.
• First-line treatment of scabies is with topical
permethrin 5% cream, which is rather effective as there is not much resistance.
• Reapplication of the cream should be performed 1week later to ensure eradication.
• Oral ivermectin can also be used as rst-line
therapy or second-line therapy if the permethrin cream does not work.
• Clothing and bedding should be washed in hot
water and dried in a hot dryer to prevent reinfestation and transmission.
Anal Intraepithelial Neoplasia
RoccoRicciardi
20
Key Concepts
• Anal intraepithelial neoplasia is a dysplastic
condition of the squamous tissue and is considered to be a premalignant stage of anal
cancer.
• The histological ndings and cellular abnormalities mirror cervical dysplasia.
• Anal cytology is a useful method to identify
anal neoplasia in high-risk groups.
• When cytology is concerning, the evaluation
of anal neoplasia can proceed with anal cytology and high-resolution microscopy, a technique similar to colposcopy.
• A targeted approach to dysplasia ablation
through microscopy is more of tissue sparing
than the historically practiced wide local excisions and ap advancements.
• Treatment should be tailored to the patient’s
degree of dysplasia, risk factors, immune status, continence, symptoms, and likelihood of
progression.
Introduction
• Anal intraepithelial neoplasia is a dysplastic
condition of the squamous tissue and is
R. Ricciardi (*)
Massachusetts General Hosptal,
Boston, MA, USA
e-mail: rricciardi1@mgh.harvard.edu
considered to be a premalignant stage of anal
cancer.
• Anal intraepithelial neoplasia (AIN) is further
stratied into three grades: AIN I, AIN II, and
AIN III, dened as low-, moderate-, and highgrade dysplasia, respectively (Fig.20.1).
• The histological ndings, including the cytologic changes, mitotic activity, nuclear membrane changes, and cellular abnormalities,
mirror cervical dysplasia grading.
• Terminology can be confusing as anal intraepithelial neoplasia is referred to by many names
including anal dysplasia, intraepithelial carcinoma, intramucosal carcinoma, squamous cell
carcinoma in situ, and Bowen’s disease.
• In addition, recently the terms high-grade
(HGAIN) and low-grade (LGAIN) anal
intraepithelial neoplasia have been proposed
that correspond to AIN III/II and AIN I,
respectively.
Symptoms
• The vast majority of individuals will experience no outward manifestation of human papillomavirus (HPV) infection, and similarly
most patients with AIN have no clear
symptoms.
• As AIN progresses to anal cancer, symptoms
become more frequently reported.
– 50% of patients with invasive cancer
describe pain and bleeding.
© ASCRS (American Society of Colon and Rectal Surgeons) 2019
S. R. Steele et al. (eds.), The ASCRS Manual of Colon and Rectal Surgery,
https://doi.org/10.1007/978-3-030-01165-9_20
277
278
Schematic representation of squamous intraepithelial lesions (SIL)
Low-grade squamous intraepithelial lesion
Condyloma
(LSIL)
CIN/AIN 1 grade 1 CIN/AIN grade 2 CIN/AIN grade 3
High-grade squamous intraepithelial lesion
R. Ricciardi
(HSIL)
Normal Moderate dysplasia Severe dysplasia
Fig. 20.1 Schematic representation of squamous intraepithelial lesions (SIL). As shown in this illustration, with
increasing severity of SIL of the anus, the proportion of
the epithelium replaced by immature cells with large
nuclear-cytoplasmic ratios increases. Invasive cancer
probably arises from one or more foci of high-grade SIL
Epidemiology
Very mild to mild dysplasia
Infection Precancer
(HSIL) as depicted in the drawing by epithelial cells
crossing the basement membrane below the region of
HSIL. (With permission from Brickman C, Palefsky JM
Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era Curr HIV/
AIDS Rep 2015;12:6–15. Copyright Springer)
– It is likely related to patient’s immune
function, subtype of HPV, repetitive inocu-
• Anal intraepithelial neoplasia develops from
HPV contact generally through direct
exposure.
• It is estimated that there are more than 100
subtypes of HPV but not all have been implicated as disease causing.
• About 90% of all patients remain asymptomatic, and those that have infection resolve
without any treatment within 2years.
• A small number of patients develop persistent asymptomatic infections, while a
smaller number of patients will develop
condyloma.
• It is unclear why a fraction of patients develop
neoplasia in the form of AIN that then may
progress to squamous cell cancer.
• Explanations for why the virus causes condyloma or neoplasia in some patients but not in
others are speculative.
lation, and/or potentially concomitant
infections such as other sexually transmitted infections.
– Among HPV subtypes, types 6 and 11,
cause 90% of genital warts as compared to
those subtypes that are associated with cancer (i.e., types 16, 18).
• HPV, the causative exposure to AIN, is quite
prevalent in both the developed and developing world.
– Estimates indicate that at any point in time,
1in 10 women worldwide harbors the HPV
virus.
– Prior to the introduction of the HPV vac-
cine, there had been a steady rise in the rate
of HPV infections across the nation and the
globe.
– However, with the introduction of the HPV
vaccine, prevalence of HPV types 6, 11, 16,
Visits (in thousands)
Year
20 Anal Intraepithelial Neoplasia
279
and 18 identied by cytology specimens
decreased by over 50% among teens and
young women.
– Genital wart cases appear to have decreased
since 2011, presumably because of
increased vaccination (Fig.20.2).
• Incidence data characterizing trends of HPV
infection and condyloma are easily obtainable, yet it is unclear whether the rate of AIN
has changed in the last several years.
– There are no public records, and cancer
surveillance data do not record incidence
or treatment of dysplastic lesions.
• National cancer incidence data do reveal that
the rate of anal cancer has been increasing for
several years; new anal cancer cases have been
rising on average 2.2% each year over the last
10years.
– The number of new cases of anal cancer
was 1.8 per 100,000 people per year based
on 2007–2011.
– Slightly more common in women than in
men.
• Much of what is known regarding the transformation of AIN to squamous cell cancer has
been extracted from the cervical cancer
literature.
– Precursor high-grade squamous intraepi-
thelial lesions.
– Integration of the viral genome into the
host occurs in order to produce genetic
change.
– Viral oncogenes are then ultimately respon-
sible for directly coupling to oncogenic
enhancers and promoters permitting continued expression through integration and
immortalization.
– Phenotypic changes of the squamous
epithelium.
– One of the most frequently reported
changes in chromosomal structure is a gain
in the long arm of chromosome 3q.
– Following incorporation of the viral
genome into host DNA, cellular changes
and atypia of squamous tissues occur.
• Ultimately these changes correspond to
AIN I which then can progress to AIN II
and AIN III and ultimately dedifferentiate into squamous cell cancer.
• It is unclear whether the development of
anal neoplasia must traverse all these
steps or if squamous cell cancer can skip
one or more phases, i.e., from AIN I
directly to AIN III.
500
400
300
200
100
0
Fig. 20.2 Genital warts. Initial visits to Physicians’ Ofces, United States, 1966–2013, http://www.cdc.gov/std/
stats13/gures/49.htm. (Source: IMS Health, Integrated Promotional Services™. IMS Health Report, 1966–2013)
1966 1971 1976 1981 1986 1991
1996 2001 2006 2011
280
Cytology
R. Ricciardi
Screening/Surveillance
• Most patients at risk for anal neoplasia
undergo screening with digital rectal examination, anal cytology, and anoscopy.
– Anal cytology is akin to cervical cytology,
providing cellular material for review of
intraepithelial lesions.
– The cytology must be performed before
any instrumentation of the anus and before
lubrication is used.
– The procedure is performed with a moist
swab in the anal canal and without any
preparation.
– Following completion, a digital rectal
examination and anoscopy can be
performed.
• The anal cytology smear is graded by a cytologist with the same classication used in gynecologic samples.
– Anal cytology may return as insufcient,
normal, atypical squamous cells of undetermined signicance, low-grade squamous intraepithelial lesion, high-grade
squamous intraepithelial lesion, or anal
cancer.
– Based on these results and prior medical
history, the recommendation is either continued surveillance or more detailed evaluation with high-resolution anoscopy.
• Lesions classied as atypical squamous
cells of undetermined signicance or
higher are generally referred for highresolution anoscopy.
• However, a large number of patients
have abnormal cytology results leading to a considerably large population of patients to evaluate in
microscopy.
• In addition, given that the sensitivity of
anal cytology ranges from 69% to 93%
and specicity ranges from 32% to
59%, results can be difcult to
interpret.
• It is important to remember that anal
cytology in high-risk cohorts such as
men who have sex with men has falsenegative rates of up to 23% in
HIV-negative patient and 45% if
HIV-positive.
• Therefore, close follow-up of all highrisk patients is likely to be the best strategy (see Fig.20.3).
• Dening the population that is high-risk and
requiring evaluation is challenging because of
societal and other behavioral concerns.
• Overall, the risk of anal neoplasia is highest in
immunosuppressed individuals as they appear
to have great difculty in clearing the virus
from their body.
Fig. 20.3 Management
algorithm for anal
cytology results. General
guidelines provided.
Individual case
management is based on
many factors, which
may increase or decrease
the interval of evaluation
Normal Insufficient ASCUS
Low risk
? unclear
Repeat cytology
6 months
Repeat cytology
12 months
LSIL HSIL
High risk
PMHx of AIN
immune-sup
High resolution anoscopy
20 Anal Intraepithelial Neoplasia
281
• Rates of anal dysplasia in HIV-infected
patients of all sexual risk groups are substantial indicating some value for anal cancer
screening in all HIV-infected patients regardless of sexual practices.
• The immunosuppressed group should also
include those with organ transplants as well as
other medically induced suppressive
conditions.
• Men who have sex with men and a concomitant diagnosis of HIV pose the greatest risk of
HPV-related illnesses and thus anal
neoplasia.
• One of the highest risk groups is women with
a past history of cervical, vulvar, vaginal, or
perineal neoplasia.
• The proximity of the anus to the vulva may
explain why patients with vulvar neoplasia
were at highest risk for anal cancer, yet the
increased risk with in situ neoplasia was also
remarkable.
• Thus, patients with gynecologic neoplasia,
and especially vulvar neoplasia, should be followed closely for potential anal cancer
development.
• Individuals with a past history of sexually
transmitted infections may also represent an
important screening population.
– A past history of condyloma is generally a
sign of prior contact with human
papillomavirus.
– At this time, it is unclear whether those
individuals who tend to develop condyloma (without any sign of dysplasia) have a
tendency to develop benign warts rather
than cancer.
• The value of anal cancer screening is difcult
to quantify.
– Screening HIV-positive homosexual and
bisexual men for anal dysplasia with anal
cytology offers quality-adjusted life expectancy benets at a cost comparable with
other accepted clinical preventive
interventions.
– Others have not come to the same conclu-
sion indicating that many of the criteria for
assessing the need for a screening program
were not met for anal neoplasia screening
and that cost-effectiveness remained
unacceptable.
– The lack of concordance for these models
may be related to the lack of agreement
with uncertainties in modeling clinical scenarios in the face of poor evidence.
– At this time, a review of 30 regional and
national guidelines for screening in HIV
patients revealed that only 2 societies recommended digital and anorectal
examination.
• The “European AIDS Clinical Society
Guidelines” recommends digital examination every 1–3years for HIV-positive
men who have sex with men.
• In NewYork State, the Department of
Health has recommended annual anal
cancer screening for HIV-positive men
who have sex with men, HIV-positive
patients with history of condyloma, and
HIV-positive women with history of
gynecologic neoplasia.
• However, the US Guidelines for the prevention and treatment of opportunistic
infections in HIV-infected adults and
adolescents recommended only an
annual digital examination for the HIVpositive population in general.
Diagnosis
• Most patients are diagnosed with anal neoplasia through investigation with digital rectal
examination, anal cytology, anoscopy, and/or
endoscopy.
– The sensitivity of digital rectal examina-
tion in identifying anal neoplasia is fairly
low as many AIN lesions are not palpable.
– Anoscopy is routinely performed by colon
and rectal surgeons and can be used to
identify macroscopic areas of AIN, which
often appear to be benign condylomata, but
may return with AIN on biopsy (Fig.20.4).
– In addition, endoscopic identication of
AIN occurs quite commonly during endoscopy, particularly during the retroexed
view of the anus.
282
Fig. 20.4 AIN 3. (Courtesy of Richard Billingham, MD)
– Last, a large number of patients are identi-
ed with anal dysplasia on cytologic evaluation during routine screening.
• During diagnostic evaluation, it is imperative
to remember that patients with AIN should
have a complete and thorough history and
physical examination.
• It is important to remember the link between
anal dysplasia with other HPV-related diseases such as oral cancer, gynecologic neoplasia, and other genital lesions.
• Following examination of the entire body, the
evaluation of AIN can proceed with anal
cytology and high-resolution microscopy, a
technique similar to colposcopy of gynecologic neoplasia.
– The colposcopic appearance of variable
grades of anal squamous intraepithelial
lesions is similar to those described for the
cervix.
– In high-resolution anoscopy, a colposcope
or other microscope is used to examine the
anal verge and anal canal in close detail.
– No bowel or anorectal preparation is neces-
sary, and the procedure is most commonly
performed without analgesia.
• After positioning, the tissues to be examined
are swabbed with a 3–5% acetic acid solution
for 2–5min.
– The acetowhitening from acetic acid with
microscopic assistance is sufcient to identify dysplastic tissues.
R. Ricciardi
– The entire anal canal and anal verge should
be examined, but we nd that dysplastic
tissues are most commonly found within
the transition zone, as this area has the
greatest area of susceptible and immature
squamous tissues.
– Dysplastic epithelium will absorb acetic
acid and appear scaly white as compared to
columnar tissues.
– The characterization of dysplastic tissue
and differentiation of AIN I, II, or III can
then be performed without biopsies and in
real time under high magnication.
– Dysplastic tissues are characterized by
scaly white plaques and with greater disarray of vascular patterns, the higher the
grade of dysplasia.
– We also nd that high-grade dysplasia
tends to be quite friable when in contact
with the anoscope or a swab (Fig.20.5).
• Some colposcopists choose to add an iodinebased Lugol’s solution to further assist with
the detection of dysplastic tissue.
– The mechanism for Lugol’s utility is that
only healthy epithelial tissue absorbs the
compound which causes normal tissue to
appear wood-like.
– Dysplastic tissues do not absorb the solu-
tion leaving these tissues with a yellowish
hue.
Fig. 20.5 AIN on high-resolution anoscopy. The pointer
denotes area of high-grade dysplasia. (Courtesy of Rocco
Ricciardi, MD)