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© Borgis - Nowa Medycyna 3/2017, s. 114-124
*Aneta Obcowska-Hamerska
Viral anal warts – current therapeutic options
Brodawki wirusowe odbytu – aktualne możliwości terapeutyczne
Department of General, Vascular and Oncologic Surgery, Czerniakowski Hospital in Warsaw
Head of Department: Professor Mariusz Frączek, MD, PhD
Streszczenie
Zakażenie wirusem HPV jest szeroko rozpowszechnioną chorobą weneryczną. Badanie fizykalne w większości przypadków jest wystarczające do rozpoznania brodawek wirusowych i rozpoczęcia leczenia. Metodę terapeutyczną dostosowujemy do zakresu i wielkości zmian oraz do preferencji pacjenta. Jako metody pierwszej linii terapeutycznej stosuje się leczenie zachowawcze: imikwimod, podofilotoksyna, sinekatechina, kwas trichlorooctowy. W przypadku nieskuteczności leczenia zachowawczego lub rozległości zmian stosuje się krioterapię, laseroterapię lub wycięcie chirurgiczne brodawek. Zmiany zlokalizowane w kanale odbytu wymagają postępowania zabiegowego. Przy braku skuteczności leczenia należy zastosować terapię łączoną, a w dalszej kolejności inne metody. Szczególną sytuację kliniczną stanowią kobiety ciężarne i osoby z obniżoną odpornością. W pierwszej grupie pewne metody leczenia są przeciwwskazane. Współistnienie stanów obniżenia odporności związane jest z obniżoną skutecznością terapii i częstymi nawrotami brodawek. U osób zakażonych wirusem HIV i leczonych immunosupresyjnie należy zwrócić szczególną uwagę na zmiany podejrzane o przemianę nowotworową i w każdym takim przypadku dokonać weryfikacji histopatologicznej. W postępowaniu z pacjentem zakażonym wirusem brodawczaka ludzkiego równie ważna co terapia jest edukacja, mająca duże znaczenie dla poprawy efektywności leczenia i ograniczenia dalszego rozprzestrzeniania się wirusa.
Summary
HPV infection is a common sexually transmitted disease. Physical examination is usually sufficient to identify viral warts and initiate treatment. The treatment method is adjusted to the extent and size of lesions as well as patient’s preferences. Conservative treatment, i.e. imiquimod, podophyllotoxin, sinecatechin, trichloroacetic acid, is usually used as first-line therapy. In the case of ineffective conservative therapy or extensive lesions, cryotherapy, laser therapy or surgical excision is used. Lesions located in the anal canal require surgical intervention. In the absence of treatment efficacy, combined treatment followed by other methods should be implemented. Pregnant and immunocompromised patients are a special clinical group. Some treatment methods are contraindicated in the first group of patients. A coexisting immune deficiency is associated with reduced therapeutic efficacy and frequent wart recurrence. Particular attention should be paid to lesions suspected of malignancy in HIV-positive patients and those receiving immunosuppressive treatment. In each such case, histopathological verification should be performed. Education, which improves treatment efficacy and limits further virus spread, is no less important than therapy in the management of patients infected with human papillomavirus.



Similarly to venereologists, dermatologists and gynaecologists, a coloproctologist surgeon is also a specialist dealing with patients affected by sexually transmitted diseases. The responsible pathogens include bacteria, viruses, protozoa, fungi and parasites. This heterogeneous group of diseases can damage many organs and systems. The human papillomavirus (HPV) is transmitted through direct skin-to-skin or mucosa-to-mucosa contact, most often during sexual intercourse, to later persist in keratinocytes. The most important risk factors include non-use of condoms and a large number of sexual partners. Proctological symptoms may occur in patients of both sexes, who are involved in different sexual practices, including anal sex. A patient presenting with genital warts may suffer from several coexisting venereal diseases, which are not always symptomatic; therefore serological testing for HIV, HBV/HCV and syphilis is advisable. Advice on the prevention of sexually transmitted infections, the need for diagnosis and treatment of sexual partners is also a good practice. It should be reported in medical documentation that this information has been provided.
HPV infection is the most common sexually transmitted disease. Up to 86% of sexually active people may be infected by the virus (1). Warts develop in only 10% of these people. The pathogen not only easily spreads, but it shows cancerogenic potential. Up to 80% of anal cancers are caused by HPV infection (2). Of the more than 100 serotypes of the virus, HPV16 is most cancerogenic for patients with perianal lesions (3). Higher rates of anal cancer are reported for homosexual men with HIV infection (46/100,000) compared to seronegative individuals (5/100,000) (4).
Diagnosis
The disease is usually diagnosed based on clinical evaluation. Macroscopic lesions are often accompanied by pruritus, burning sensation, less commonly by pain, wet feeling in the anus or blood staining. Physical examination should begin with abdominal and inguinal evaluation. Visual inspection of the genitals and the anus should be supplemented with anal palpation and anoscopy. Single or multiple papular, papillous lesions with a tendency to merge into one another, which may exfoliate and are located in the genital or anal area, are a typical symptom of HPV infection. Although biopsy and histopathological examination are not required to confirm the diagnosis, they become necessary in the case of atypical lesions, ulcerations, bleeding and tissue discolouration, as well as in immunocompromised patients. Histopathological verification should be also contemplated at further stages, in the absence of improvement or clinical picture deterioration despite treatment. Gynaecological consultation and cytology should be recommended in each woman with viral anal warts.
Treatment
The onset of symptoms may occur many months after exposure. In about 1/3 of patients, symptoms may resolve spontaneously within 4 months, whereas in other cases the disease remains stable or multiple new lesions develop (5). Since it is impossible to estimate which patients are classified into the first group, treatment should be offered to all patients (6). Absence of evident symptoms does not indicate the lack of infectiousness. It is estimated that the risk of infecting a sexual partner persists for 6 months after symptom resolution. The patient should be also warned that the symptoms may recur, particularly during periods of reduced immunity (due to infection, increased physical exercise or sunlight exposure).
The treatment of viral warts involves chemical and surgical destruction as well as immune therapy. The choice of method depends on, among other things, the size and extent of lesions, comorbidities, patient’s preferences and consent to the proposed therapy. In this regard, both the possibility and regularity of local application of medications as well as patience in waiting for the disappearance of warts and knowledge of the potential complications of method used are also important. Extensive, merging lesions located in the perianal region or in the anal canal are an indication for surgical treatment. Further part of the paper describes different methods for the treatment of HPV infection, starting from first-line therapies.
Imiquimod is a substance whose efficacy is mainly due to modulatory effects on the immune response by stimulating macrophages and monocytes to produce interferon α and cytokines, mainly IL-12 and TNF-α. It is usually used as 5% (Aldara) or 3.75% cream (Zyclara). The 5% imiquimod cream is applied 3 times a week prior to normal sleeping hours. The cream should be left on for 6 to 10 hours and then removed by washing with water. The therapy should be continued for 16 weeks or until warts disappear. The lower concentration formulation is to be used daily for 8 weeks. The efficacy of 5% imiquimod cream is 35-75%, with recurrence rates of 6-26% (7, 8). Although studies indicate lower efficacy of the 3.75% cream, shorter treatment duration is its advantage (9). The medication causes a number of local adverse effects, such as reddening, irritation, erosions and ulceration. These symptoms usually resolve after treatment discontinuation, allowing the patient to resume the therapy. Local symptoms may be accompanied by flu-like manifestations. The cream may reduce the efficacy or local contraceptives during the application period.
Podophyllotoxin in the form of 0.5% solution (Condyline) and 0.15% cream (Wartec) has antimitotic activity. The preparation is applied twice daily for 3 consecutive days. The remnants of the drug should be washed off after 4 hours. The 3-day treatment cycle should be repeated after a 4-day interval, which may be repeated four times. The skin around the lesions should be protected against active substance, e.g. by applying a protective layer of vaseline. Sexual contacts should be discontinued during therapy. According to a systematic literature review, the efficacy of podophyllotoxin in the form of solution and cream is 45-83% and 43-70%, respectively (7). Local irritation is more common and may be more severe compared to imiquimod. Symptoms are most severe in the first treatment period. Podophyllotoxin often causes headache.
Sinecatechin used in the form of 10 or 15% ointment (Veregen) is an antiviral substance derived from green tea extract. It most probably acts by influencing apoptosis and genes whose products modulate antiviral responses. The ointment is applied on the affected anoderm three times daily, without the need to remove the remaining formulation before another application. The efficacy of the ointment (10 and 15%) shown in randomised trials in the treatment of external genital and perianal warts is up to 58% throughout the treatment group (surprisingly higher among women – 65%), with only minor local adverse effects (10, 11). The need for long-term treatment is a disadvantage of this drug (12).

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otrzymano: 2017-07-06
zaakceptowano do druku: 2017-07-27

Adres do korespondencji:
*Aneta Obcowska-Hamerska
Klinika Chirurgii Ogólnej, Naczyniowej i Onkologicznej Szpital Czerniakowski Sp. z o.o. w Warszawie
ul. Stępińska 19/25, 00-739 Warszawa
tel. +48 (22) 318-63-35
aneta_w@poczta.onet.pl

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