The Effectiveness of Chemical Cautery and Electrosurgery on Anogenital Wart: Systematic Review

Introduction

Anogenital warts (AGW) or condyloma acuminata, is one of the sexually transmitted infections (STIs) resulting from human papillomavirus (HPV) which manifest as fibroepithelial hyperplasia of skin or mucous membrane. Anogenital warts are a fairly common condition in sexually active adults with an annual incidence rate of 2%.¹ Anogenital wart treatment aims to eradicate lesions and prevent their recurrence with minimal side effects. The therapeutic modality is classified into pharmacological such as chemical cautery with trichloroacetic acid (TCA) and non-pharmacological such as electrosurgical excision.²

The highly recommended therapy for AGW is chemical cautery by using TCA with a concentration of 70–100%. It is easy to apply with minimal side effects such as pain and burning sensation. Previous studies reported that chemical cautery using TCA was effective for superficial lesions with the cure rate ranging from 70% to 80% and recurrence rate was 36%.³ Another commonly used modality treat AGW is electrosurgery. It is effective for small warts on penis, vagina or rectal region, but big lesions must be avoided, as it may lead to a scar formation. A randomized controlled trial study stated that the cure rate of electrosurgery for AGW treatment was 94% at the sixth week.⁴ Appropriate management is required to the effectiveness and reduce the recurrence rate as well as side effects. Hence, we conducted this systematic review to compare the efficacy of chemical cautery using TCA to electrosurgery in AGW.

Methods

This systematic review was according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and no registered to the International Prospective Register of Systematic Review (PROSPERO).

Search Strategy

The search was conducted for studies assessing chemical cautery using TCA for AGW treatment from January 2013 to March 2023, with the following keywords: ((Anogenital warts) OR (Genital warts) OR (Condyloma acuminata) OR (Human papillomavirus) OR (HPV)) AND ((chemical cautery) OR (trichloroacetic acid) OR (TCA)) AND ((Therapy) OR (Treatment)), ((Anogenital warts) OR (Genital warts) OR (Condyloma acuminata) OR (Human papillomavirus) OR (HPV)) AND ((Electrosurgery) OR (Electrosurgical)) AND ((Therapy) OR (Treatment)) (Table 1). The investigators independently searched throughout several databases including PubMed and the Cochrane Library. Decisions were recorded through Microsoft Excel.

Table 1 MeSH Terms Retrieved in Articles

Study Eligibility Criteria

In terms of studies eligibility, we only included studies which met the inclusion criteria, namely (1) type of study (clinical trials, randomized control trial, case series); (2) study population (anogenital warts patients, age <18 years old and >18 years old); (3) intervention (chemical cautery, electrosurgery); and (4) outcomes (cure rate, recurrence rate, side effects). Meanwhile, the exclusion criteria were irretrievable full text and language other than English.

Data Extraction

A predetermined outcome sheet in Microsoft Excel was used to include the following data to be extracted: (1) author and year of publication; (2) study design; (3) study location; (4) time to follow-up; (5) study population (number of population, sex, mean age, number of lesions, and site of lesion); (6) intervention (type of intervention and duration); (7) outcome (cure rate and recurrence rate). Cure rate as the main outcome, was defined as lesions which were successfully eliminated or when the size of the wart reduced but did not disappear. Moreover, recurrence rate was defined by the presence of new warts after achieving complete response.

Results

Search Selection and Characteristics

Literature search flow details were described in Figure 1.⁵ A total of 982 articles were found upon initial search, removed 70 duplicates then screened and retrieved 913 articles. After being assessed for eligibility, 13 studies were included in this systematic review consisting of retrospective study (n=6), randomized control trial (n=5), and quasi-experimental (n=2). The most common retrospective study was conducted in 629 patients and total of 945 patients were included in this study (346 patients received chemical cautery using TCA and 598 patients treated with electrosurgery). The mean age of this subject was 34.27 years old. The duration of chemical cautery treatment range from 2 to 24 weeks.

Figure 1 PRISMA chart. Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. International Journal of surgery. 2021; 88: 105906. Creative Commons.5

Study Outcomes

The summary of the outcome of each study was listed in Table 2 and Table 3. The cure rate of chemical cautery of TCA varied ranging from 20% to 94.1% while the cure rate of electrosurgery was between 28% and 100%. The recurrence rate of chemical cautery and electrosurgery after 1-year follow-up was 27.6% and 14.6% respectively. Numerous adverse effects of electrosurgery were reported include bleeding and scar formation with the most common adverse effect was pain sensation. Meanwhile, the most common reported adverse effect of chemical cautery with TCA were pain and burning sensation.

Table 2 Articles Addressing of Trichloroacetic Acid (TCA)

Table 3 Articles Addressing of Electrosurgery

Discussion

The management of patients with AGW focuses on eliminating wart and precancerous lesions. The therapeutic modalities are topical therapy, systemic therapy, and destructive and surgical therapy.¹⁷ Topical therapy can be carried out by administering podophyllin, podophyllotoxin, 5-fluorouracil, imiquimod, and cidofovir.¹⁸ Podophyllin and podophyllotoxin is an antimitotic agent, 5-fluorouracil is DNA and RNA synthesis inhibitor, imiquimod is immunomodulator, and cidofovir is antiviral.^19–24 Apart from topical therapy, AGW management can also be done with ablative techniques such as destructive therapy and surgery. Destructive and surgical therapy for HPV can be performed through trichloroacetic acid (TCA), cryotherapy, carbon dioxide (CO₂) lasers, photodynamic therapy (PDT), and excision surgery.^22,23 Destructive and surgical therapy have the same main mechanism of action, which is to induce tissue damage and thereby remove AGW lesions.^25–27 Administering retinoids, cimetidine, interferon, or vaccines are systemic therapy for HPV.²⁸ Retinoid is an antioxidative and keratolytic agent, cimetidine is an immunomodulator, interferon is an immunomodulator and could suppress cell proliferation, and vaccine is a prophylactic measure.^29–31

Trichloroacetic acid acts as a cytotoxic agent causing coagulation of superficial tissue to cauterize damaged tissue.^22,23 Trichloroacetic acid is one of the recommended clinic-based treatments. It is one of the chemical peels-based methods used in AGW management. It is usually used in high concentration preparations of 80–90%.^32,33 For superficial skin lesions it may use pure TCA 10–30%, or in a combination form, such as TCA 15% combined with lactic acid 10%, or TCA 15% combined with salicylic acid (SA) 15% and lactic acid 15%. Trichloroacetic acid works by forming coagulation of epidermal proteins and keratinocytes.³³ Higher concentrations of TCA solutions result in better clinical improvement.³⁴ However, in this systematic review, it was discovered that a high level of effectiveness was not found to be associated with higher TCA concentrations or longer duration of therapy, whereas 70% TCA for 3 months had a greater effectiveness rate (94.1%) compared to that of TCA 100% with a duration of 6 months (82.2%). This effectiveness was also influenced by the number of lesions and the TCA application technique. Application technique is very important because the depth of penetration depends on the quantity of application. TCA is commonly used in several consecutive applications.^13,33

Anogenital wart therapy using TCA commonly required several consecutive applications.³⁵ Although it has a fairly high effectiveness, the recurrence rate in TCA therapy is also quite high, reaching 36%.³⁶ In this systematic review, the recurrence rate ranged from 2.9% to 33%. These recurrence rates were time-dependent, in which, higher recurrence was found in a longer duration of follow-up time of 6 months, and higher TCA concentrations (100%). The recurrence rate at the same lesion site reached 61.1%.¹¹ The study also discovered that the most common side effects of TCA were discomfort, burning sensation, pain and bleeding. These side effects relate to post-application peeling.³³

Electrosurgery utilizes alternating current to produce different types of waveforms producing a combination of excision and coagulation that usually requires local anesthesia. Direct contact with skin causes coagulation and drying without carbonization (electrodesiccation), while air gaps (usually 1–3 mm) are used to cause rapid heating and carbonization of tissue (electrofulguration). The dry tissue that subsequently appears is removed by curettage.³⁷ Another approach utilizes high-frequency alternating electric currents that pass through the lesions causing immediate tissue damage.³⁸

The effectiveness rate of electrosurgery in AGW is very high, reaching 94–100%.³² This study obtained an effectiveness rate between 33.5% and 100%. The highest level of effectiveness was found in male subjects and mean age of 38.4 years. Among other therapeutic modalities for AGW, surgery is the most effective treatment to reduce the risk of recurrence after complete clearance.³⁹ The electrosurgery was higher when compared to that of TCA in a 1-year follow-up period. The recurrence rate of electrosurgery in a 1-year follow-up period was 8%, while the TCA recurrence rate for the same follow-up period was 27.6%.

Electrosurgery has a higher effectiveness rate and lower recurrence rate compared to TCA. However, electrosurgery has more severe side effects when compared to TCA, in which bleeding predominantly occurs in electrosurgery. In addition, an RCT study reported that electrosurgery has a lower tolerance level when compared to TCA (79.4% vs 85.5%). Other benefits of using TCA are that it is easier and cheaper because it does not require local anesthesia or complicated technical equipment so that it can be performed on an outpatient basis, and TCA does not cause tissue evaporation which may increase the risk of HPV exposure for clinicians performing the procedure.⁴⁰

Several factors have been correlated to AGW recurrence including the patient’s immune defense. The inability of the immune system to recognize an incoming or descending virus can be explained by the nature of the virus lifecycle. HPV infects basal cells and expresses of the early viral genes which are responsible for replication, transcription and stimulation of cell proliferation. In addition, the late gene that allows replication and encapsulation of viral DNA, and capsid structural proteins is expressed in the granular layer. During natural infection, viral antigens are not effectively presented to the immune system, nor can they be expressed at levels detectable by the immune system. This may lead to ineffective T cell activation leading to a lack of immunological ignorance and/or tolerance of virus-infected cells.⁴¹ Another study reported that patients with genitourinary infections are prone to AGW recurrence due to repeated stimulation of the skin and mucosa by various pathogens resulting in an increase of HPV colonization. The number of skin lesions are an independent influencing factor for AGW recurrence which causes declinine in the immune system to inhibit and eradicate HPV by T lymphocyte cells.⁴²

Conclusion

In conclusion, electrosurgery has a better effectiveness as well as lower recurrence rate. However, electrosurgery can cause more serious side effects, has more complex applications and increases the risk of exposure to HPV for clinicians conducting the procedure.