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Human Papillomavirus, Condylomata Acuminata, and Anal Neoplasia

Article · November 2004

DOI: 10.1055/s-2004-836942 · Source: PubMed

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Human Papillomavirus, Condylomata
Acuminata, and Anal Neoplasia
George J. Chang, M.D.1 and Mark L. Welton, M.D.2

ABSTRACT

Genital human papillomavirus (HPV) infection is an increasingly common

sexually transmitted disease. This virus causes condylomata acuminata and is associated
with anal neoplasia. Management options are discussed.

KEYWORDS: Human papillomavirus, condylomata acuminata, anal neoplasia

Objectives: Upon completion of this article, the reader should be familiar with human papillomavirus and understand the management
of condylomata acuminata.

HUMAN PAPILLOMAVIRUS INFECTION HPV infection is extremely common in the cervix

Genital human papillomavirus (HPV) infection is in- and affects between 2% and 43% of the female popula-
creasingly common and affects an estimated 24 million tion worldwide.6 In the United States, the prevalence
Americans.1 It is the most common sexually transmitted is 22.5% overall and significantly higher among the
disease and is second only to human immunodeficiency young.7 The prevalence of HPV infection among
virus (HIV) infection in causing morbidity and mortal- 600 young women attending family planning clinics
ity. Perianal HPV infection produces a wide range of in an urban setting was 82%.8 In another study of over
disease presentations, from asymptomatic infection to 2011 young women aged 15 to 19, the 3-year cumulative
benign genital warts to invasive cancer. risk of acquiring HPV infection was 44%.9 Clearly, not
Human papillomaviruses are members of the all of these individuals go on to develop cervical cancer,
Papovaviridae family of epitheliotropic double-stranded and in fact HPV infection in most women demonstrates
DNA viruses and are considered tumor viruses because a pattern of regression or latency with HPV DNA
of their ability to immortalize normal cells. Currently becoming undetectable even by polymerase chain
more than 130 types of HPV have been identified, reaction (PCR) assays by 1 to 2 years.10 Only a small
with more than 40 types infectious for the lower genital percentage of women develop persistent and progressive
tract, of which  15 are oncogenic.2 These are generally disease. Other cofactors such as smoking, history of
characterized as ‘‘low-risk’’ types (6, 11, 42, 43, 44), sexually transmitted infections, and individual immune
which are primarily associated with genital warts and responses to HPV may be necessary along with onco-
respiratory papillomatosis, or as ‘‘high-risk’’ types (16, genic HPV infection for carcinogenesis.
18, 31, 33, 35, 39, 45, 51, 52), which are associated with The true prevalence of anal HPV infection in the
low-grade and high-grade squamous intraepithelial general population is not currently known, but it is
lesions (LSIL and HSIL) and invasive cancer.3–5 present in virtually all HIV-positive men who have sex

Sexually Transmitted Diseases of the Colon, Rectum, and Anus; Editor in Chief, David E. Beck, M.D.; Guest Editor, Mark L. Welton, M.D.
Clinics in Colon and Rectal Surgery, volume 17, number 4, 2004. Address for correspondence and reprint requests: George J. Chang, M.D.,
Department of Surgical Oncology, Unit 444, U.T. M.D. Anderson Cancer Center, 1400 Holcombe Blvd., FC 12.3004, Houston, TX 77230-1402.
E-mail: gchang@mdanderson.org. 1Department of Surgical Oncology, U.T. M.D. Anderson Cancer Center, Houston, Texas; 2Division of Colon
and Rectal Surgery, Department of Surgery, Stanford University, School of Medicine, Stanford, California. Copyright # 2004 by Thieme Medical
Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. 1531-0043,p;2004,17,04,221,230,ftx,en;ccrs00190x.
221
222 CLINICS IN COLON AND RECTAL SURGERY/VOLUME 17, NUMBER 4 2004

with men (85 to 93%) and also in a high proportion of to have a prevalence of  20 million.1 It is the most
HIV-positive injection drug users who did not engage in common anorectal infection affecting homosexual
anal-receptive intercourse (46%).11 Anal HPV preva- men.18 However, it also frequently occurs in bisexual
lence is more common HIV-positive men, at more than and heterosexual men and women. Although the most
60%, versus 17% in HIV-negative men. Another risk common mode of transmission is through sexual con-
factor for HPV infection is the number of sexual part- tact,19,20 nonsexual routes of transmission via fomites
ners. Up to two thirds of sexual partners of patients and nonsexual contact can also occur.21,22
with condylomata acquire HPV infection. Among HIV- Anal lesions occur most frequently in men who
negative homosexual men, the prevalence of anal HPV engage in anal-receptive intercourse, where the associa-
infection has been reported to be as high as 78% by tion has been observed to be as high as 95% in pa-
PCR.12 In an earlier study of 71 heterosexual male tients.23–25 However, there is significant variability in
patients with anal fissure or hemorrhoids in a surgical this association and the presence of anal condylomata
outpatient department, the incidence of cytologic evi- does not necessarily imply that a patient engages in anal-
dence of anal HPV infection was 25%. This figure rose receptive intercourse. The virus pools in the vagina and
to 98% in 225 men seen for anal condylomata.13 Ad- at the base of the scrotum and penis from where it can
ditionally, infection by multiple HPV types is common track along the perineum to the anus. Patients who are
and carries an increased risk for anal squamous intra- immunosuppressed are also at higher risk. Following
epithelial lesions (SIL, also known as anal intraepithelial renal transplantation the anal condylomata incidence has
neoplasia or AIN) and progression to HSIL over time. been reported to be 2.4% to 4%.26
Multiple HPV types were found in 73% of HIV-positive In HIV-positive patients the HPV prevalence is
and 23% of HIV-negative homosexual men.14 30%.27 The effect of HIV infection on the course of
Women with cervical HSIL are also at a high risk HPV disease is unclear but may be influenced by the
for anal HPV infection (51%) when compared with severity of immunocompromise and the use antiretro-
control women without cervical intraepithelial neoplasia viral therapy. Infection by high-risk HPV types is
(CIN) (14%). This control group is validated by a 24% associated with SILs, which are the putative precursors
prevalence of cervical HPV infection which is compara- to invasive cancer. The impact of HIV on HPV infec-
ble to the general population.15 In a subsequent study of tion, as well as the associated biologic and behavioral risk
women with invasive vulvar cancer, histologic evidence factors in patients with HIV and HPV, may contribute
of anal HPV-16 infection was identified in 48.5% of to the 30- to 80-fold higher rates of anal cancer in HIV-
patients with vulvar cancer versus 13.7% of control positive patients versus the general population.28–30
women with no prior history of anogenital HPV infec-
tion or neoplasia.16 In a San Francisco cohort study of
319 at-risk young women (high-risk for HIV), the SYMPTOMS
prevalence of anal HPV infection by PCR was 76% Most patients with anal condylomata present with minor
among HIV-positive women and 42% of HIV-negative complaints. The most frequent complaint is that of
women.17 perianal growth. Pruritus ani may be present and to a
The actual prevalence of anal HPV infection will lesser degree, discharge, bleeding, odor, tenesmus, and
depend upon the sum effect of risk factors such as difficult perianal hygiene may be noted.
smoking, number of sexual partners, sexual behavior,
presence of other sexually transmitted diseases (STDs),
and so on. But it may be in the range of 5 to 15% in DIAGNOSIS
women, with autoinoculation being a potentially signi- Physical examination may reveal the classic cauliflower-
ficant mechanism, and the range may be somewhat lower like lesion (Fig. 1). The warts tend to run in radial rows
in men. These figures would explain the reason for the out from the anus and may be surprisingly large at the
higher prevalence of anal cancer in the general popula- time of presentation. Macroscopically the warts may vary
tion of women than in men. Improving sensitivities of from lesions invisible to the naked eye to pinhead-sized
the tests for HPV DNA detection in recent years should lesions to large cauliflower-like masses. The warts
be considered when examining the data prior to second- may be single or multiple, or coalesce to form polypoid
generation hybrid capture or PCR. masses. Individual warts can be sessile or pedunculated,
isolated, or clustered. Anoscopy and proctosigmoi-
doscopy are essential because the disease extends inter-
CONDYLOMA ACUMINATA nally in more than 75% of patients and in up to 94% of
Genital warts, or condylomata acuminata, are now homosexual men.18 Lesions are often found on the
the most common virally transmitted STD, surpassing perianal skin or within the anal canal and lower rectum.
even genital herpes. Condylomata acuminata affects They are pink or white in color. Microscopically, anal
 5.5 million Americans each year and is estimated warts show acanthosis of the epidermis with hyperplasia
 HPV, CONDYLOMATA ACUMINATA, ANAL NEOPLASIA/CHANG, WELTON 223

Table 1 Treatment of Condyloma Accuminata

Folklore Charming
Hypnosis
Lime water
Lemon juice
Topical Methods Podophyllin
Podophyllotoxin
Trichloroacetic acid
Bichloroacetic acid
5-fluorouracil
Dinitrochlorobenzene
Fowler’s solution
Phenol
Cochicine
Dimethyl sulfoxide
Tetracycline ointment
Figure 1 Anal condylomata accuminata. Bismuth sodium triglycollamate
Thiotepa
Sulfonamide cream
of prickle cells, parakeratosis, and an underlying chronic Ammoniated mercury
inflammatory cell infiltrate. Serologies and cultures for Idoxuridine
HPV and other venereal diseases may be taken from the Bleomycin
penis, anus, mouth, and vagina and the PCR technique Cantharidin
can be used to detect HPV DNA with high sensitivity. Solcoderm
The differential diagnosis includes condylomata Immunologic Methods Imiquimod
lata and anal squamous cell carcinoma. Condylomata lata Interferon
are the lesions of secondary syphilis. They are flatter, Bacille Calmette-Guerin
paler, and smoother than condylomata acuminata. Anal Autovaccination
squamous cell carcinoma is generally painful and may be Surgical Techniques Excision
tender and ulcerated where condylomata are not tender Electrocautery fulguration
or ulcerated. Laser therapy
Infrared coagulation
Cryotherapy
TREATMENT Liquid nitrogen
Due to the risk for communicability, as well as the risk Carbon dioxide snow
for the development of squamous cell carcinoma, lesions Liquid air
should generally be treated. Many methods of treating
Currently utilized techniques are in italics.
condylomata acuminata have been described and are
listed in Table 1. In general they can be separated into
topical, immunotherapeutic, and surgical techniques. podofilox, which is the best-characterized and most
We prefer to examine the patient in the prone-jack- active component against genital warts.32 It is applied
knifed position. But lateral decubitus, lithotomy, and in a vehicle such as liquid paraffin or tincture of benzoin.
knee-chest positions all provide adequate exposure. Podophyllin has the advantage of being simple to use
Excellent lighting is imperative and a magnifying device and it is inexpensive. Concentrations of 5 to 50% have
may be helpful. been used without much difference in efficacy.33–36
Podophyllin is applied directly to the warts with care
to avoid the adjacent normal skin because it is extremely
Topical Chemical Agents irritating.
Several disadvantages, including application limi-
PODOPHYLLIN tations, limited efficacy, and systemic toxicities, have led
Podophyllin is the best-known and most widely available to podophyllin losing favor as a treatment modality for
topical chemical agent. First recommended for the anal condylomata. It must be washed off after 6 hours
treatment of condylomata by Culp and Kaplan in because it is extremely irritating to the surrounding
1942,31 it is a cytotoxic agent derived from the resin of normal skin and causes a severe local reaction that can
Podophyllum emodi and Podophyllum peltatum that con- include dermatitis, necrosis, scarring, or fistula in ano.37
tains biologically active lignin compounds, including It cannot be applied to internal lesions. It is rarely
224 CLINICS IN COLON AND RECTAL SURGERY/VOLUME 17, NUMBER 4 2004

effective after a single application and multiple treat- trial, demonstrate modest and variable efficacy when
ments require repeated visits to the office. It also has compared with placebo.51,53,55,57 Although complete
poor penetration into keratinized warts, decreasing its remission rates of 82% have been reported,56 the overall
efficacy. Response rates are variable but can be as low success and 6-month recurrence rates are  50% and
as 22% after 3 months of therapy.35 Use of podophyllin 25%, respectively.58
during pregnancy has been associated with teratogenicity Many authors have advocated the use of inter-
and intrauterine fetal death.38 Systemic toxicities to feron in combination with other therapeutic modalities59
virtually all of the organ systems can occur with applica- for extensive, refractory disease and to improve wart
tion of large amounts of podophyllin.39–41 Finally, the clearance rates. Aside from the adverse effects noted
potential for oncogenicity cannot be overlooked. above, interferon has the disadvantage of high cost and
Podophyllotoxin is one of the active compounds potentially decreased efficacy with concurrent HIV dis-
in podophyllin. It is effective in wart clearance in about ease.60 At this time, interferon has not gained wide
one half of cases, but is associated with a high recurrence acceptance for the treatment of anogenital condylomata
rate. Its advantage is that it is safer and can be self- and has widely been supplanted by the use of imiquimod.
administered.42,43
IMIQUIMOD
BICHLORACETIC ACID OR TRICHLORACETIC ACID Topical imiquimod is an immune modulator that in-
Bichloracetic acid is a powerful keratolytic and cauterant duces interferon and cytokine release by the host tissues.
and has been successfully used for the management of Although it has no direct antiviral activity, it activates
condylomata.23 Like podophyllin, it is inexpensive and the host immune system to clear the HPV infection by
easily applied. It has the advantage of being applicable both the innate and cell-mediated pathways. Applied as
to internal disease. However, it too can cause local a 5% cream, external wart clearance can be achieved in 72
skin irritation and often requires multiple office visits, to 84% of women and a somewhat smaller percentage of
generally at weekly intervals. In an uncontrolled study by men. It is well tolerated and safe, with the most frequent
Swerdlow and Salvati, bichloracetic acid was compared side effect of treatment being local erythema. Once the
with other modes of office-based therapy and noted to lesions have been cleared the local recurrence rate has
result in better patient comfort and decreased recurrence been reported to be 5 to 19%.61 Although controversial,
rates.23 there may be a role for adjuvant imiquimod treatment
following surgical therapy of condylomatous disease.
CHEMOTHERAPEUTIC AGENTS
Various chemotherapeutic agents used for the treat- VACCINE
ment of condylomata have been described, including In 1944, Biberstein first described the use of immu-
5-fluorouracil (5-FU) as a cream or salicylic acid notherapy with an autologous vaccine in the treatment
preparation,44–46 thiotepa,47 bleomycin,48 dinitrochlo- of condylomata acuminatum.62 Although efforts have
robenzene in acetone,49 and idoxuridine cream.50 Un- been made for a vaccine,24 they have not been widely
fortunately, most descriptions are anecdotal for the effective. More recently, HPV vaccines targeting the
treatment of anal warts and there are no meaningful late structural proteins of the viral capsid (E6, E7) have
reports of efficacy. shown more promise. The ideal vaccine engenders a cell-
mediated immune response generating HPV-specific
cytotoxic T-lymphocytes. Since cross-reactivity among
Immunotherapy HPV subtypes is low, newer approaches are geared
toward generating polyvalent vaccines. In preclinical
INTERFERON animal models, both prophylactic and therapeutic
Interferons are produced and secreted in response to viral vaccines have effectively induced HPV-specific cell-
infections. Thus interferon injection may be a practical mediated immune responses. Although safety and
way to treat refractory anogenital warts.51 Intramuscular, immunogenicity of vaccine preparations have been
intralesional, and topical therapies have all been em- demonstrated in Phase I trials, few data exist on efficacy
ployed,51–55 but it is generally felt that the systemic route and there are multiple trials ongoing.63,64
is ineffective. The usual dose of intralesional interferon is
1 to 2 million units. Ten to 28 days of daily treatment
have been reported.56 However, the usual maximum Surgical Therapy
dose per patient is 5 million units due to adverse effects
such as fever, chills, myalgia, headache, fatigue, and ELECTROCOAGUATION
leukopenia. Therefore the maximum number of warts Electrocautery is an effective way to destroy both inter-
that can be injected at one time is 5.45 Multiple trials, nal and external anal warts but this technique requires
including a randomized double-blinded multicenter local anesthesia and is somewhat dependent on the skill
 HPV, CONDYLOMATA ACUMINATA, ANAL NEOPLASIA/CHANG, WELTON 225

of the operator who must control the depth and width of condylomata. Care is taken to avoid injury to the under-
the cauterization. The effect is a first- or second-degree lying sphincter mechanism. Although most patients can
burn. Controlling the depth of the wound is important have all of their disease removed in one procedure,
to prevent scarring and injury to the underlying anal patients with more extensive disease may require staged
sphincters. Circumferential burns should be avoided excisions at an interval of 1 to 3 months.74 The advan-
to prevent anal stenosis. If the disease is extensive or tage of this approach is that it allows for pathologic
circumferential, efforts should be made to preserve skin examination of the specimen. In prospective, rando-
bridges. If this is not possible, treatment should be mized, controlled trials comparing simple surgical exci-
staged. In studies of electrocoagulation, complete clear- sion to 25% podophyllin for up to 6 weeks, rates of wart
ance was achieved in up to 94% with a recurrence rate of clearance and recurrence were significantly better with
22%.46 Close follow-up is needed to identify recurrent simple excision.33,75
disease that can often be treated topically in the office.
Representative biopsies should be taken at the time of
electrocoagulation for pathologic evaluation for dysplasia RECURRENCE
or occult carcinoma. The problem of recurrence is a significant one in
the treatment of condylomata and rates have been
LASER THERAPY reported to range between 4.6% to over 70% depending
Carbon dioxide laser therapy to destroy condylomata was on the treatment modality.23,24 Although current efforts
first reported by Baggish in 1980.65 An overall success are aimed at removing or destroying all visible warts,
rate of 88 to 95% has been reported.66,67 This is similar little is known about subsequent transmission or per-
to electrocautery, but laser ablation has a higher recur- sistence of papillomavirus in the tissues. The problem of
rence rate and is associated with as much or more recurrence is a multifaceted one that must take into
postoperative pain.66 With respect to treatment efficacy, consideration surgical technique, surveillance, immuno-
laser therapy has no benefit over conventional electro- competence, and patient behavior. Incomplete treat-
cauterization68 and is limited by higher equipment costs ment, particularly due to presence of internal disease
and the potential for aerosolization of virus in the laser or disease that is not visible to the unaided eye, causes
plume,69,70 which can result in laryngeal papillomatosis self-inoculation and recurrence. Furthermore, warts are
in the operating surgeon.71 caused by the papillomavirus and eradication of virus
from any tissue is problematic. For this reason, addition
CRYOTHERAPY of immunotherapy after surgical ablation is an attractive
Cryotherapy involves the topical application of liquid concept that may gain favor as experience with immu-
nitrogen, carbon dioxide snow, or liquefied air to the notherapy grows.76 In particular the treatment margins
warts. This technique purportedly does not require are at greatest risk for recurrence. In addition many
anesthesia but this is not the general experience. Post- patients are immunocompromised either from HIV or
treatment pain levels are comparable to electrocautery immunosuppressive agents. Adding to the complexity of
and laser therapy. In head-to-head trials comparing this issue is the fact that sexual partners of patients with
cryotherapy to trichloroacetic acid72 or to electro- genital HPV are also likely to have genital HPV. Failure
cautery,73 no difference in efficacy was found. Rates of to treat a partner’s lesions is also a cause of recurrence. It
success are reported to be 63 to 88% with recurrence of is generally felt that a 3-month disease-free interval is
warts in 21 to 39% of patients.46 These rates are inferior safe for resumption of sexual activity.
to those achieved with electrocautery.

SURGICAL EXCISION ANAL NEOPLASIA

Surgical excision has long been used to treat condylo- Anal SILs are an increasingly prevalent condition asso-
mata acuminata with superior rates of treatment success ciated with HPV infection and condylomata and can
and recurrence. Patients are placed in the prone, jack- occur both externally and internally within the anal
knife position and their buttocks taped apart for expo- canal. SILs range from low- to high-grade and the
sure. Classically a solution of 1:200,000 epinephrine progression to high-grade dysplasia (HSIL) may be an
in saline or lidocaine is injected subcutaneously and intermediate stage toward malignant transformation to
submucosally to separate the warts and facilitate the squamous cell carcinoma of the anus.
preservation of healthy skin and mucosa. The wart is The principle risk factor for anal neoplasia is
grasped with a pair of toothed forceps and excised with the presence of HPV infection. Cofactors include anal-
fine scissors. Electrocautery may be used for hemostasis receptive intercourse and immunocompromise. It is now
or as an adjuvant modality. apparent that infection by oncogenic strains of the HPV
The combination of excision and electrocautery is may be causative for the development of anal cancer.77,78
considered to be the gold standard for the treatment of HPV infection is also causative in the development of
226 CLINICS IN COLON AND RECTAL SURGERY/VOLUME 17, NUMBER 4 2004

anal SIL (also known as anal intraepithelial neoplasia or and anal disease processes support the argument that
AIN) and there is also growing evidence that invasive screening followed by directed ablative therapy may have
anal cancer is preceded by the development of HSIL. a beneficial effect on anal cancer. Histological simi-
These findings parallel observations in the cervix where larities between anal HSIL and cervical HSIL with
HPV infection causes the development of CIN, the regard to angiogenesis, increased cellular proliferation,
precursor lesion to invasive cervical cancer.79 Although and decreased apoptosis have been demonstrated.84
limited data exist on the natural history of anal HPV As seen with CIN, anal LSIL can regress or
infection and the development of anal cancer, multiple progress to HSIL. However, HSIL does not typically
epidemiological and associative studies have demon- revert to LSIL or normal without treatment. Moreover,
strated an HPV/anal SIL/anal cancer relationship that although either LSIL or HSIL may be the presenting
appears to mimic that for cervical cancer.80 phenotype, LSIL does not directly go on to become
invasive cancer without progressing to HSIL. In the
cervix, 21% and 0.15% of CIN I lesions progress to CIN
The Cervical-Anal Analogy III and invasive cancer, respectively.85 In the anus, 50%
The natural history of untreated anal SIL is unknown. of HIV-negative homosexual men who had LSIL had
However, there are many similarities between the cervix regression of their lesions over a 2-year period. However,
and the anus suggesting that the lessons learned from 62% percent of HIV-positive and 36% of HIV-negative
treatment of cervical dysplasia may be applicable to anal men with LSIL progressed to detectable HSIL within
dysplasia. Anal cancer and cervical cancer are caused by the same time period. Anal SIL and HSIL developed
HPV infection, and the observed relationship between within 2 years in 17% and 8% of HIV-negative men who
HPV, HSIL, and squamous neoplasms of the anus is had no evidence of lesions at baseline, respectively.86,87
similar to that of the cervix where the etiologic relation- The 4-year incidence of HSIL in HIV-negative men was
ship between HPV infection, cervical HSIL, and cervical 17%.28 These numbers are consistent with findings from
cancer has been established. Seattle where HSIL developed in 15% and 5% of HIV-
Numerous similarities exist between the cervix positive and HIV-negative men, respectively.88 Factors
and anus. Both tissues are exposed to trauma from activ- in progression may include multiplicity of oncogenic
ities such as defecation, receptive anal intercourse, and HPV-type infection and HPV viral activity as well as
vaginal intercourse. Both cancers are histologically simi- cigarette smoking and host immunity. Thus, the similar-
lar and have a tendency to arise from the squamous- ities between anal and cervical neoplasia make the
columnar transformation zone. Both the anus and cervix cervical SIL/cancer sequence a reasonable model for
have a similar anatomic feature, the transformation zone the study of anal carcinogenesis, and consideration
(the squamocolumnar transitional zone of the anal canal must be given to screening and treatment for anal SIL
and the cervical transformation zone) where squamous as is done for cervical SIL.
metaplasia is found. The immature squamous metaplas-
tic cells of these transformation zones are the most
susceptible to oncogenic HPV, although the nonkerati- Bowen’s Disease and HSIL
nizing and keratinizing squamous epithelium of the Bowen’s disease, squamous cell carcinoma in situ, is
surrounding tissues are also susceptible. HSIL in both often an incidental finding discovered at the time of
tissues is associated with HPV infection ( 61% of anal histological evaluation of an anal specimen obtained
HSIL have HPV DNA).17,28,81 Under the microscope, at surgery for an unrelated diagnosis. It is considered
cervical SIL and anal SIL are virtually indistinguishable. premalignant. It is generally treated by mapping with
There is also morphologic and histological similarity punch biopsies taken in a clock-face pattern at 1-cm
between cervical and anal cancer. Cervical cancer is intervals from the anus, as described by Strauss and Fazio
preceded by a well-defined precursor lesion, CIN, or in 1979.89 Wide excision of affected tissue is performed
more generally SIL of the cervix. based on intraoperative frozen section analysis of the
Although there is a relative abundance of data on punch biopsies, and skin flaps are often mobilized for
the benefits of screening and treatment of CIN, there are closure of the skin defects. Large amounts of uninvolved
limited data about the natural history of HSIL and the tissue may be sacrificed to obtain clear margins because
effectiveness of ablative therapy.82,83 But cervical Pap the lesions are not grossly apparent. The recurrence
smears and ablative therapy, although never subjected to rate with wide excision is 23.1% and the cancer rates
trials, have proven effective for the prevention of cervical are less than 10%.90,91 Postoperative continence, steno-
cancer. Prior to the implementation of these interven- sis, and resumption of sexual activity rates have not been
tions, the incidence of cervical cancer was 36 per reported.
100,000. But with the introduction of screening techni- Although Bowen’s disease is surgically treated
ques, the incidence of cervical cancer has decreased by with wide excision of the perianal skin and anal mucosa,
78%.84 The numerous similarities between the cervical disease above the dentate line in the transformation zone
 HPV, CONDYLOMATA ACUMINATA, ANAL NEOPLASIA/CHANG, WELTON 227

is often left untreated. The transformation zone is com-

posed of variable amounts of transitional epithelium and
rectal mucosa with squamous metaplasia. Metaplastic
tissue is an immature tissue and may be particularly
susceptible to HPV infection. Thus, the standard ther-
apy for anal Bowen’s disease may leave in situ the tissue
most at risk for development of malignancy.
Within the treating community (surgeons, gyne-
cologists, dermatologists, primary care physicians)
there is considerable disagreement as to how Bowen’s
disease and HSIL should be treated, partly because they
are considered by many to be different diseases. There-
fore, we sought to establish how Bowen’s disease might
be distinguished from anal HSIL. In our series of
10 patients diagnosed with Bowen’s disease at other
institutions, histologic evidence of HPV infection was
present in all 10 specimens. Moreover, they were other-
Figure 2 Areas of dysplasia appear white and display charac-
wise histologically indistinguishable from HSIL.92 teristic vascular markings after the application of 3% acetic acid.
Further, upon immunohistochemical study, Bowen’s
disease and high-grade SIL both have statistically signi- dysplasia, either from previous biopsy or Pap smear, are
ficantly increased microvessel density and show similar ‘‘mapped’’ in the operating room with the operating
trends in apoptosis and proliferation rates when com- microscope, acetic acid, and Lugol’s solution. The pa-
pared with normal tissue. Thus, Bowen’s disease and tient is positioned and a perianal block given as described
HSIL are indistinguishable histologically and immuno- earlier. The anal canal and perianal skin are painted
histochemically. It seems reasonable to consider review- with 3% acetic acid and examined with the operating
ing the terminology and standardizing treatment of the microscope. Tissue infected with HPV becomes white
‘‘two diseases’’ for consistency. Currently, histopatholo- (acetowhite) and demonstrates characteristic vascular
gists and dermatopathologists use the term Bowen’s patterns94 allowing otherwise occult disease to be iden-
disease, a term that probably should be avoided, while tified (Fig. 2). The tissues are next painted with Lugol’s
cytopathologists label the same findings as HSIL. solution. Nonkeratinizing high-grade lesions of the anal
This leads to unnecessary confusion among treating canal do not readily take up Lugol’s solution and stain
physicians. either mahogany or yellow. Low-grade and normal
tissues stain partially or completely black (Fig. 3). The
high-grade–appearing lesions are biopsied and the lesion
TREATMENT is destroyed with electrocautery. Electrocautery ablation
Patients with anal SIL present with minor complaints
and are typically identified during evaluation of anal
condylomata or pruritus. They may demonstrate typical
condylomatous lesions or simply abnormal-appearing
anal canal mucosa. The perianal skin and the entire
surgical anal canal, as defined by the American Joint
Committee on Cancer and by the World Health Orga-
nization, extending through the length of the internal
anal sphincter to the anal verge (2 to 4 cm in women, up
to 6 cm in men) should be thoroughly examined.
Patients with low-volume disease and no history
of dysplasia may be treated with topical agents in the
office regardless of risk factors. The primary care physi-
cians perform follow-up screening Pap smears. Patients
with large-volume disease are treated in the operating
room with a combination of excisional or incisional
biopsy and cautery destruction under monitored anes-
thetic care with a standard perianal block as previously
Figure 3 Normal tissues and areas of low-grade dysplasia
described.93 The pathology is reviewed for evidence of take up Lugol’s solution and appear black. Areas of high-grade
dysplasia. The primary care physician performs a follow- dysplasia do not take up Lugol’s solution and appear yellowish or
up Pap smear at 3 months. Patients with a history of light tan (here grayish or lighter).
228 CLINICS IN COLON AND RECTAL SURGERY/VOLUME 17, NUMBER 4 2004

is achieved by ‘‘painting’’ the lesion with needle tip and effective treatment for controlling HSIL in the
cautery. The surgeon moves the needle tip quickly across general population and appears to be effective in the
the tissue trying not to burn deeply, as this damages the immunosuppressed patients as well, but multi-institu-
underlying tissues unnecessarily, potentially increasing tional trials may be needed to establish its impact on anal
scarring and hemorrhagic complications. The lesion and cancer.
a small 2- to 10-mm rim of tissue are destroyed in this
fashion. Care is taken to preserve normal-appearing
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