|Year : 2021 | Volume
| Issue : 1 | Page : 52-55
Evaluation of human papillomavirus in skin tags
Magda M Haggag1, Azza G. A. Farag1, Shymaa A El-Askary2, Mai E. K. Ahmed3
1 Department of Dermatology, Andrology and Sexually Transmitted Diseases, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Dermatology, Andrology and Sexually Transmitted Diseases Department, Samanod Hospital, Gharbia, Egypt
|Date of Submission||09-Jun-2019|
|Date of Decision||09-Jul-2019|
|Date of Acceptance||14-Jul-2019|
|Date of Web Publication||27-Mar-2021|
Mai E. K. Ahmed
El-Mahallah El-Kubra, Gharbia
Source of Support: None, Conflict of Interest: None
Skin tags (STs) are flesh-colored, pedunculated growths, with a smooth surface. The etiology of STs is still obscured. Human papillomavirus (HPV), a small DNA virus of papovavirus family, has been implicated in the causation of STs.
To detect the relationship between HPV skin infection and STs.
Patients and methods
Patients with STs (n = 80) and age-matched and sex-matched healthy controls (n = 40) were enrolled in this case–control study. From each patient, one skin biopsy was taken from STs lesions and another one from the perilesional skin (5 cm away from STs), and from each control, site-matched punch skin biopsy was taken. PCR was used to detect HPV DNA in every tested sample.
HPV positivity showed a significant stepwise upregulation from normal skin (4, 10%), passing by STs perilesional (10, 12.5%) and ended by STs lesional (38, 47.5%) specimens (P < 0.001).
HPV has a role in the pathogenesis of STs. Therefore, using of antiviral or immunotherapy may help in STs management program.
Keywords: human papillomavirus, PCR, skin tags
|How to cite this article:|
Haggag MM, Farag AG, El-Askary SA, Ahmed ME. Evaluation of human papillomavirus in skin tags. Menoufia Med J 2021;34:52-5
| Introduction|| |
Skin tags (STs), or acrochordons, are common, small, soft, usually pedunculated benign skin growths , mostly presented in intertriginous area, for example, axilla, neck, and eye lid . STs have an incidence of 46% in the general population  and are very common in middle-aged and elderly individuals . STs usually vary in diameter from 2 to 5 mm, although larger STs up to 5 cm in diameter are occasionally evident .
Clinically, STs manifested as three types: multiple small papule, single or multiple filiform protrusions, or solitary bag-like pedunculated lesions . Histologically, STs are polypoid growths with overlying mildly acanthotic epidermis and a fibrous vascular kernel dermis .
The etiology of STs is still unknown . Some of the associated factors are frequent irritation of the skin , obesity, metabolic syndrome, and hormonal imbalance  as well as human papillomavirus (HPV) skin infection .
HPV is a small DNA virus of papovavirus family. Demonstration of the existence of HPV in the tissues depends on the identification of viral nucleic acids by PCR than serological methods, which cannot distinguish between present and past infection of HPV .
In this study, we tried to find any relation between HPV skin infection and development of STs.
| Patients and methods|| |
This case–control study was conducted on patients (n = 80) having variable numbers of STs lesions. They were compared with age-matched and sex-matched healthy volunteers (n = 40) as a control group. Patients were recruited from the Outpatient Clinic of Dermatology, Andrology and Sexually Transmitted Diseases Department, Menoufia University Hospital, during the period from September 2017 to June 2018. A written informed consent form was signed by each participant included in this study after informing them about the study. The study was approved by the Ethical Committee of Human Right of Research at Menoufia University, which was in accordance with Helsinki Declaration 1975.
We included patients with STs, older than 15 years, of both sexes. Any patient having verrucae anywhere in the body was excluded from the study.
All enrolled participants were subjected to medical history and thorough clinical examination . Full dermatological examination was done including determination of site, number, and distribution of STs .
A total of 200 biopsies were collected. From each patient, excisional biopsy of one ST (80 lesional biopsies) and 4 ml punch biopsy of nonlesional skin, 5 cm away from the excised ST (80 perilesional biopsies) were done. From the control group, site-matched 40 punch biopsies were obtained. All specimens were obtained under aseptic condition and local anesthesia. Then the specimens were collected in sterile container with saline and refrigerated at −20 to −80°C till time of analysis. PCR was performed to detect presence of HPV.
PCR and genomic DNA extraction were performed as follows: the DNA extraction kit used was supplied by Thermoscientific (Sigma, Cairo, Egypt), and the manufacturer's recommendations were followed. DNA sequence files for HPV types 6 and 11 were obtained from Genbank (http://www.ncbi.nih.gov/genbank/) (Sigma) [Table 1] .
PCR was carried out in a 25-μl reaction volume, containing 1 μl (~50 ng) of extracted DNA, 1 μl of each pair of primers, 12.5 μl of 2 × Taq premix Mastermix (Sigma), and 9.5 μl sterile double-distilled water. The PCR program involved an initial denaturation step at 95°C for 5 min followed by 35 cycles of a denaturation step at 95°C for 30 s, a primer annealing step at 54–56°C for 30 s, an extension step at 72°C for 30 s, and a final extension step at 72°C for 10 min All PCR products were analyzed by running 10 μl of the product on 1% (w/v) agarose (Sigma) by gel electrophoresis performed at 4 V/cm in Tris borate EDTA buffer [TAE buffer (0.5 mol/l Tris acetate, 5.7% acetic acid, 10 mmol/l EDTA pH 8.0] containing 0.5 μg/ml ethidium bromide ( Innogenetics N.V., Ghent, Belgium) stained with 0.5 μg/ml ethidium bromide, and photographed under a UV transilluminator by using a Digital Kodak Science 120 system (Eastman Kodak, Rochester, New York, U.S). A DNA ladder digest of 1 kb (GeneRuler 50 bp DNA; Fermentas Life Sciences, Thermo Fisher Scientific, Waltham, Massachusetts, USA) was used as a molecular weight marker. A positive control represented by β-actin gene and a negative control without a DNA template were included .
Data were collected, tabulated, and statistically analyzed by statistical package for the social science software (SPSS) statistical package version 20 (IBM, Armonk, NY, USA) on IBM compatible computer. Two types of statistics were done: descriptive statistics were expressed as mean ± SD as well as median and range for quantitative data or number and percentage for qualitative data, and analytic statistics, where χ2-test was used to study the association between two qualitative variables. Student's t-test was used to compare normally distributed quantitative variables in two groups. Mann–Whitney test (nonparametric test) is a test of significance used for comparison between two groups of not normally distributed quantitative variables. Value of P less than 0.05 was considered statistically significant.
| Results|| |
Demographic characteristics of the studied patients are demonstrated in [Table 2]. Patients with STs and control patients were comparable regarding their age, sex, and BMI. However, family history of STs was significantly higher in STs patient group (P = 0.002; [Table 2]). Clinical characteristics of patients with STs are shown in [Table 3].
|Table 2: Comparison between the two studied groups regarding demographics data|
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PCR results of investigated patients were as follows: gel electrophoresis PCR studies of HPV [Figure 1] revealed that HPV positivity showed a significant stepwise upregulation from normal control skin (4, 10%) passing by perilesional (10, 12.5%) and ended by lesional (38, 47.5%) specimens (P < 0.001; [Table 4]).
|Figure 1: Gel electrophoresis PCR of human papillomavirus types 6 and 11 and β-globin. Lane L: 100–1000 DNA ladder size marker. Lanes 3–5 show the 103 bp band specific for human papillomavirus 6, lane 9 shows the 159 bp band specific for human papillomavirus 11, and lane 1 shows the 364 bp band specific for β-actin.|
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|Table 4: Comparison between the different studied groups according to human papillomavirus positivity|
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Additionally, the lesional STs specimens demonstrated a significant high HPV positivity than the perilesional and normal ones (P = 0.001 and 0.004, respectively). However, the difference between perilesional and control specimens could not reach level of significance [Table 4].
| Discussion|| |
The clinical condition of STs is closely similar to that of mucocutaneous papillomatosis and their clinical behavior may be reminiscent of that of laryngeal papillomas, with respect to the fact that they spread locally in the same patient, which might raise the suggestion of a common aetiology. As HPV has been identified in many papillomas, it may consequently be responsible for the development of STs .
Therefore, this study was designed to shed light on the possible role of HPV in etiopathogenesis of STs, through evaluation of HPV DNA in STs by using PCR.
In this study, PCR as a sensitive and specific method for detection of viral DNA in tissues was used to search for HPV DNA in STs lesions. A positive control represented by β-actin gene to ensure the quality of DNA sample and the absence of PCR inhibitors was used .
Of the current 40 investigated control samples, four (10%) demonstrated HPV positivity. Supporting this finding, Foulongne et al.  reported that cutaneous HPV is a part of the microbiological flora of the healthy human skin. Moreover, in a study done by Astori et al. , they were able to detect HPV DNA in 35% of normal skin samples, suggesting that HPV DNA may be widely distributed in normal skin of immune-competent individuals in whom intact immune system inhibits the development of disease.
In this study, there was a significant difference in HPV positivity between the studied groups, which showed stepwise upregulation from normal skin (10%) specimens, passing by perilesional (12.5%) and ended by lesional (47.5%) tissues. Therefore, we confirmed the possible role of HPV in the pathogenesis of STs.
The result of this study was in accordance with a study done by Gupta et al. , who previously reported the presence of HPV DNA in 48.6% of biopsies taken from 37 Indian patients. Moreover, our results coincided with that of Karayana et al. , who studied 16 Indonesian patients. The authors reported 14 (46.7%) positive samples out of the total 30 ST lesions. However, Dianzani et al.  reported the presence of HPV in 88% of ST samples that were obtained from 49 White patients. This higher prevalence was also reported by Sallam et al. (76.6%)  and Askar et al. (71.4%) . The presence of HPV DNA in STs suggests the possible role of these viruses in their development. On the contrary, the lack of viral transcripts could indicate a latent infection by HPV .
STs are known to develop in areas of skin friction, leading to disruption of skin, which might serve as a route of entry for the virus. The existence of HPV DNA and mechanical friction seem to be significant cofactors in the STs pathogenesis .
There was no conflict between the being of HPV part of the microbiological flora of the healthy human, as we mentioned to explain the results of positive cases of the control groups, and the role of HPV in STs pathogenesis, which is confirmed by the significant difference in HPV positivity between the studied groups. The possible role of HPV in STs development has been postulated to friction and abrasion, which leads to denudation of the basement membrane and access of the virus to the basal cells. HPV infection begins with the inoculation of the virus into the interrupted epithelium and the interaction with a putative specific cellular receptor . HPV infection involves squamous epithelium and can cause growth stimulation, cell proliferation, and the formation of pathologic cells  through the role of E5 oncoprotein, which can activate growth factor receptors . So the existence of HPV DNA alone cannot begin the infection, as it needs a route of entry caused by other factors like friction and abrasion.
As previously reported , we observed that there was no significant relation between HPV positivity and the site of the ST. Moreover, in agreement with Gupta et al. , we concluded that HPV positivity is independent of patient's sex, which is indicated by the absence of the relationship between sex of patients with STs and the presence of HPV infection in this study.
| Conclusion|| |
In this study, the presence of HPV in the ST lesions from different sites could be a contributing factor in the development of STs, supporting its role in the pathogenesis of these cutaneous lesions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ramachandrareddy D, Prathap R. Human papilloma virus (HPV) causing skin tags. J Evol Med Dent Sci 2013; 2
Iacopi E, Riitano N, Coppelli A, Goretti C, Piaggesi A. Diabetes and the skin. Clin Dermatol Res Ther 2018; 2
Jusuf NK, Putra IB, Kartayana J. The correlation between body mass index with the occurrence of skin tag. Open Access Maced J Med Sci 2017; 5
Ma H, Xia Y, Yin S, Lai W. Giant skin tag on the labium majorum. Int J Womens Dermatol. 2015; 1
Shashikala P, Nandyal SS, Sawkar S. Achrochordon infected with human papilloma virus. J Pup Health Med Res 2014; 2
Abdou AG, Maraee AH, Antar AG, Fareed S. Role of mast cells in skin tag development: an immunohistochemical study. Anal Quant Cytopathol Histpathol 2014; 36
Putra IB, Siregar R, Jusuf NK, Ginting O, Nurhayati R. Correlation between serum leptin level with type and number of lesion skin tag. Open Access Maced J Med Sci 2019; 7
El Safoury O, Abdel Hay R, Fawzy M, Kadry D, Amin IM, Abu Zeid OM, Rashed LA. Skin tags, leptin, metabolic syndrome and change of the life style. Indian J Dermatol Venereol Leprol 2011; 77
Idris S, Sunitha S. Assessment of BMI, serum leptin levels and lipid profile in patients with skin tags. J Clin Diagn Res 2014; 8
Askar H, Darwish N, Abdelgaber S, Eldomiaty A. Human papilloma virus in skin tags. Egypt J Med Microbiol 2016; 25
Molijn A, Kleter B, Quint W, van Doorn LJ. Molecular diagnosis of human papillomavirus (HPV) infection. J Clin Virol 2005; 32
Sari R, Akman A, Alpsoy E, Balci MK. The metabolic profile of patients with skin tags. Clin Exp Med 2010; 10
Farag AGA, Badr EA, Eltorgoman AMA, Assar MF, Elshafey EN, Tayel NR, Aboutaleb HE. Role of 11β HSD 1, rs12086634, and rs846910 single-nucleotide polymorphisms in metabolic-related skin diseases: a clinical, biochemical, and genetic study. Clin Cosmet Investig Dermatol 2019; 12
Sallam MA, Kamel MM, El Missiry AG, Helal MF. Detection of human papilloma virus DNA in skin tag. Sci J Al-Azhar Med 2003; 24
Foulongne V, Sauvage V, Hebert C, Dereure O, Cheval J, Pariente K, et al
. Human skin microbiota: High diversity of DNA viruses identified in the human skin by high throughput sequencing. PLoS One 2012; 7
Astori G, Lavergne D, Benton C, Hockmayr B, Egawa K, Garbe C, de Villiers EM. Human papillomaviruses are commonly found in normal skin of immunocompetent hosts. J Invest Dermatol 1998; 110
Gupta S, Aggarwal R, Gupta S, Arora SK. Human papillomavirus and skin tag: is there any association? Indian J Dermatol Venereol Leprol 2008; 74
Karayana J, Jusuf NK, Putra IB. Identification of HPV types 6 and 11 in skin tags using PCR. Stem Cell Oncol 2018; 3
Dianzani C, Calvieri S, Pierangeli A, Imperi M, Bucci M, Degener AM. The detection of human papillomavirus DNA in skin tags. Br J Dermatol 1998; 138
Dianzani C, Paolini F, Conforti C, Silvestre M, Flagiello F, Venuti A. Human papillomavirus in skin tags: a case series. Dermatol Pract Concept. 2018; 8
Morshed K, Polz-Gruszka D, Szymanski M, Polz-Dacewiz M. Human papillomavirus (HPV): structure, epidemiology and pathogenesis. Otolaryngol Pol 2014; 68
[Table 1], [Table 2], [Table 3], [Table 4]