Should patients with anogenital warts be tested for genital herpes? Initial results of a pilot study

© Our Dermatol Online 4.2019 329 How to cite this article: Tamer F, Yuksel ME, Avcı E. Should patients with anogenital warts be tested for genital herpes? Initial results of a pilot study. Our Dermatol Online. 2019;10(4):329-332. Submission: 07.12.2018; Acceptance: 10.02.2019 DOI: 10.7241/ourd.20194.2 Should patients with anogenital warts be tested for genital herpes? Initial results of a pilot study


INTRODUCTION
Sexually transmitted diseases like genital wart, genital herpes, syphilis, human immunodeficiency virus (HIV) infection remain a worldwide public health problem [1]. Hepatitis B has also been regarded as a sexually transmitted infection for years. Hepatitis C virus can be transmitted sexually especially in HIV positive patients [2]. Sexually transmitted diseases affect both men and women during the reproductive years. Most of the patients with sexually transmitted diseases (86%) are between the ages of 15 to 29 [1]. Genital warts are caused by human papillomavirus (HPV) which is the most common sexually transmitted virus worldwide. More than 200 types of HPV have been described yet and for about 40 types of HPV can lead to benign or malign lesions in the genital area [3]. It has been suggested that over 99.7% patients with cervical cancer had positive HPV test results [4]. Genital warts may coexist with other sexually transmitted diseases. Therefore, appropriate screening for sexually transmitted diseases is recommended in all patients presenting with genital warts [4].
Genital herpes is the most common genital ulcerative disorder primarily caused by herpes simplex virus type-2 (HSV2) or herpes simplex virus type-1 (HSV1) [5]. Herpes simplex virus type-2 is shed in the genital tract asymptomatically. Transmission of the virus usually occurs during periods of asymptomatic viral shedding [6].
Interaction between HPV and HSV has been associated with cervical carcinogenesis. Herpes simplex virus infection and replication may induce cytopathic effects in HPV-positive tissues [7]. Herpes simplex virus type-2 infection is considered as a facilitative factor in cancer development [8]. Sexually transmitted disease prevention and treatment programs are crucial to reduce the transmission of these infections [9].

MATERIALS AND METHODS
The study included 20 patients with genital warts and 20 healthy individuals within the control group. Medical records of the participants were reviewed retrospectively between May 2017 and May 2018. The exclusion criteria were pregnancy, immunosuppression, malignancy and conditions which require regular blood transfusions like anemia, thrombocytopenia, hemophilia and chronic kidney disease.
Laboratory tests including serum levels of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), hepatitis C antibody (anti-HCV), anti human immunodeficiency virus antibody (anti-HIV), herpes simplex virus type-1 (HSV1) IgG and herpes simplex virus type-2 (HSV2) IgG were evaluated in each participant. Venereal Disease Research Laboratory (VDRL) test results were evaluated in patient group.
All patients with genital warts were treated with cryotherapy. The therapy was performed every three weeks, for a maximum of five treatment sessions. The patients were adviced to use mupirocin 2% cream twice daily, after the cryotherapy treatment.
Data were analyzed using SPSS 20.0 Statistical Package Program. Descriptive statistics were presented as number and percentage for classified data, and as mean ± standard deviation or median (minimum; maximum) for numerical values. The chi-square test was used to compare categorical variables between patient group and healthy individuals. As the numerical variables were not normally distributed, groups were compared using non-parametric tests. Differences between two independent groups were tested with Mann Whitney U test. The p-value <0.05 was considered significant.

RESULTS
The study included 20 patients with genital warts and 20 healthy individuals within the control group. Each group consisted of 17 (85%) male and 3 (15%) female participants. The mean age of the patients was 30.8±8.2 (range: 20-52). The mean age of the healthy individuals was 31.6±9.7 (range: 19-58) (p=0.9).
The mean disease duration of the patients with genital warts was 6.6±6.5 months (range: 1-24 months). Twelve (60%) patients did not receive any treatment previously. One (5%) patient used topical imiquimod 5% cream (Aldara ® ) three times per week for two months. Seven (35%) patients were treated with 1 to 5 sessions of cryotherapy twice monthly.
Venereal Disease Research Laboratory test was nonreactive in all patients with anogenital warts ( Table 1).
The mean serum HBsAg level was 0.32±0.15 S/CO in patients (range: negative <1, positive>1 S/CO). The mean serum HBsAg level was 0.23±0.04 S/CO in healthy individuals (p=0.03). Serum HBsAg levels were negative in all patients and healthy individuals.
T h e m e a n s e r u m a n t i -H B s l e v e l w a s 305.44±391.64 mIU/mL in patients (range: negative: 0-10, positive: 10-1000 mIU/mL). The mean serum anti-HBs level was 83.88±99.82 mIU/mL in healthy individuals (p=0.29). Serum anti-HBs levels were positive in 15(75%) patients and negative in 5(25%) patients. Serum anti-HBs levels were positive in 14(70%) healthy individuals and negative in 6(30%) healthy individuals (p=1).
The mean serum anti-HCV level was 0.06±0.02 S/CO in patients (range: negative: 0-1, positive: 1.45-1000 S/CO). The mean serum anti-HCV level was 0.05±0.02 S/CO in healthy individuals (p=0.78). Serum anti-HCV levels were negative in all patients and healthy individuals.

DISCUSSION
Genital warts (condylomata acuminata) are manifestations of a sexually transmitted disease usually caused by HPV type 6 and 11. Genital warts are more common in men than in women. They usually present as multiple, asymmetric, exophytic lesions, plane papules or cauliflower-like growths in the anogenital region [10]. In addition, genital warts may occur as a giant mass which is called Buschke-Loewenstein tumor [11]. The diagnosis of genital wart is usually made based on clinical findings. However, a biopsy should be performed to painful, bleeding, ulcerated and therapy-resistant lesions in order to reach a definitive diagnosis [10]. The differential diagnosis should include verrucous cancer of the vulva, condyloma lata, skin tag, lichen planus, sebaceous cyst and pearly penile papules [10,12]. Treatment of choice includes topical use of podophyllotoxin, imiquimod and trichloroacetic acid, electrocauterization, cryotherapy, laser therapy and surgical excision [13]. Cryotherapy is one of the most commonly used and effective method with low complication rates [14]. However, surgical excision is needed for large and resistant warts, also for lesions suspicious for malignancy, and for warts which cause obstruction [15].
Genital warts may also be the manifestations of high-risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52) which are associated with low/high grade squamous intraepithelial lesions and invasive cancer. The relationship between HPV infection and cervical cancer has been well established. Moreover, oncogenic strains of HPV play role in the development of anal cancer. Genital warts can be localized both externally and internally within the anal canal and lower rectum. Therefore, cervical pap smear, anoscopy and proctosigmoidoscopy are essential in the management of patients with anogenital warts [16].
Patients with genital warts should be screened for coinfections with other sexually transmitted diseases [17]. Herpes simplex virus type-2 plays a synergetic role with HPV in the development of malignant changes in HPV-positive tissues [7,22]. Transmission of HSV2 to an uninfected individual usually occurs during asymptomatic reactivation of the virus. Antiviral treatment may decrease the incidence of HSV2 infection by preventing HSV2 shedding [6]. Within this study, detection of positive serum HSV2IgG levels were statistically more frequent in patients with genital warts compared to healthy individuals. These results suggest that screening of patients with genital warts for genital herpes may be helpful in the management of HSV2 spreads and cytopathic effects of co-infection of HSV2 and HPV.
Hereby, the preliminary results of laboratory tests for the evaluation of patients with anogenital warts have been reported. Further studies with larger sample size are required to confirm our data.

Statement of Human and Animal Rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Statement of Informed Consent
Informed consent was obtained from all patients for being included in the study.