Efficacy of Surgical vs. Conservative Treatment in HPV Plantar Warts: A Cohort Study

ABSTRACT

Background and Aim

Plantar warts are a high reason for consultation in our daily clinic. There are multiple and varied treatments to eliminate this viral tumor in the foot, although each treatment also presents different results and effectiveness. The goal was to compare the efficacy of surgical treatment vs. conservative treatment of plantar warts, in aspects such as treatment time and number of cures.

Methods

This was a cohort study with a sample of 72 lesions (N = 72). The effectiveness of plantar wart surgery was evaluated and compared to conservative treatments (nitric acid, bleomycin, and a combination of both). Conservative treatments were applied once a week until complete healing. The surgical removal of the wart and its closure was a secondary intention.

Results

Overall, 30% of the injuries were treated surgically and the rest conservatively. The clinical resolution varied between 4 and 393 days, with a mean of 51.8 (SD 65.9) days. Conservative treatment times increase by 1.9 days compared to the surgical recovery time, which on a practical level means 21.9 days compared to 70.1 days.

Conclusion

The excision of the plantar wart reduces the duration of the treatment by around 50% compared to conservative treatments; these findings could be considered in clinical practice when choosing a treatment.

Summary

• Plantar warts are solitary, deep, and painful lesions. Most common skin injury on the foot.

• There are multiple conservative treatments, but without consensus and with different results. Various studies suggest that surgery could be more effective.

• The objective is to compare the effectiveness of surgical treatment vs. conservative treatment.

• Case–control study (N = 72), with 30% surgery and the rest as bleomycin, nitric acid, or a combination of both.

• The lesions have an average size of 3.9 mm, and the average treatment time is 51.8 days.

• Wart surgery reduces resolution times by 50% regardless of location and size.

1. Introduction

The human papillomavirus (HPV) is characterized by producing proliferative lesions on the skin and mucous membranes of humans. Currently, more than 200 genotypes have been described, and associated with various injuries and/or diseases, each of which can cause different clinical forms [1, 2, 3, 4]. One of these manifestations is plantar warts, frequently associated with HPV genotypes 1, 2, 4, 5, 10, 14, 19, 20, 27, 57, and 65 [3, 4, 5, 6]. The annual incidence of plantar warts is 14% [5]. Its highest peak incidence is between 6 and 16 years of age [6, 7]. Plantar warts are solitary, deep, and painful lesions that appear on non‐hairy skin. In addition, warts are usually located in pressure areas, with a size between 2 and 6 mm. Characteristically, they have two distinct clinical features identity: (1) they are covered by a layer of hyperkeratotic tissue and (2) they possess a central area with black dots due to the presence of thrombosed capillaries of the warty stroma [8, 9, 10].

There are various possible treatments, but with no broad therapeutic consensus since the outcomes have diverse rates of effectiveness [11]. However, there are some common treatments that are applied by podiatric professionals, such as salicylic acid, cantharidin, bleomycin, nitric acid, and laser ablation. Some other treatments are less conventional in the context of daily clinical practice, such as imiquimod or radiofrequency [12]. There is a consensus on what can be considered an ideal treatment: being effective, painless, inexpensive, and leaving no scar [1, 8]. Some authors refer to a therapeutic scale that goes from least to most aggressive [11, 13]. In the first step, salicylic acid is located; in the second step, cryotherapy, bleomycin, laser ablation, and cantharidin are used. Finally, surgical removal is the last option [13].

Surgery is a modality that many authors describe solely and exclusively in rescue or last‐choice cases. However, various studies have suggested that surgery could be more effective than the above‐mentioned conservative treatments [9, 10, 11, 12, 13, 14, 15, 16], although current evidence has not yet clarified this aspect. For this reason, the present study aimed to compare the effectiveness of surgical treatment vs. conservative treatment, such as nitric acid, bleomycin, and the combination of both, for plantar warts, in aspects such as treatment time and number of cures, with the hypothesis that surgical treatment could be effective in such outcomes.

2. Methods

There is a retrospective cohort study using data collected at the University Podiatry Clinic of the University of Valencia between 2015 and 2023. One group or cohort received conservative treatment, while the other received surgical treatment. The study adhered to the ethical principles established in Helsinki and complied with current data protection regulations, in addition to having authorization from the Universitat de València Ethics Board number H1544963805733, in charge of supervising ethical and scientific aspects in research, which allowed the collection of clinical data for scientific purposes, with exemption from informed consent due to the retrospective study design.

2.1. Data Collection and Procedures

The data were extracted by the principal investigator, who anonymized the records at source through numerical coding. Data were extracted from the medical records of 72 subjects, according to the sample size estimation made a priori, and presented later in this writing. The records had to correspond to subjects who met the diagnosis of a solitary plantar wart, treated with surgical or conservative treatment, and who adhered to the treatment, that is, compliance with the scheduled number of sessions. The diagnosis was clinical with the dermatoscope. The most characteristic clinical signs are: the appearance of a halo hyperkeratosis with disappearance of dermatoglyphs and visualization of thrombosed capillaries “little black dots,” and the presence of dermal papillae [17]. Patients diagnosed with mosaic warts, with surgical lesions treated by first intention closure (suture), with recurrent lesions, and/or whose complete data were not available, were excluded. In addition to the sociodemographic variables related to sex, weight, and age, the variables of laterality of the condition, plantar location, size of the lesion, type of treatment, that is, classified as conservative or surgical, date of admission and discharge, and duration of treatment were collected. Finally, the need for follow‐up assistance and the number of necessary cures were also collected. All patients were also analyzed during Weeks 4–6 after discharge to assess the presence of recurrences.

Regarding patients who opted for the conservative solution, the topical treatment applied was chosen under the optional decision between bleomycin, nitric acid, or a combination of the two. All conservative treatments are carried out once a week until healing and before their application, the hyperkeratotic tissue surrounding the plantar wart is removed. As for the nitric acid, it is applied with a soaked swab for about 20–30 s on the injury and allowed to dry. This 60% acid solution is marketed directly in the master formula to podiatrists for clinical use. Bleomycin solution is dropped on the wart and “picked” into the wart using a needle. This technique was described by Munn et al. [18], and no more than 0.1 mL of the solution is applied. Bleomycin is a drug that is available to the professional during consultation. The combination of the two is first performed with bleomycin and then sealed with the application of nitric acid.

If, on the other hand, the patient opted to perform the surgical excision of the lesion, the entire pre‐surgical protocol established at the University Podiatry Clinic was carried out. Surgical removal of the wart is performed as a whole, leaving a couple of millimeters of safety margin. A hemostatic plug is applied to act as a stopper for the first 48 h, and then the cavity closure by second intention of the surgical wound was performed.

2.2. Data Analysis

The extracted data were tabulated in an Excel sheet, in which the variables were represented in columns and each patient in rows. A descriptive synthesis of the subjects' characteristics was carried out, using means, standard deviations, frequencies, and contingency tables. The subjects were classified according to the surgical or conservative treatment of choice. Additionally, participants were subclassified by the type of agent used to eliminate the condition, such as bleomycin, nitric, or a combination of both. The condition was classified by its size, while the location was classified by region, as shown in the image, to obtain a sufficient sample in each of the groups: first ray, toes, metatarsal heads, plantar vault, or heel (see Figure 1).

Figure 1.

Classification of the parameter “plantar wart location” by region: first ray, toes, metatarsal heads, plantar vault, or heel.

An inferential analysis was carried out with the R software, version 3.2.2, using the lubridate and ggplot2 libraries, consisting of an association study to determine the correlations between age, diameter of the lesion, treatment time, and number of cures through Pearson tests. To assess the possible relationship between treatment time and location, the Kruskal–Wallis test was performed. Finally, a log‐linear model assessed whether there was a statistical association between treatment time, type, and location.

An a priori sample size calculation was carried out to be able to test the hypothesis with a Type I error of less than 5% (α = 0.005) and a study power greater than 85% (β = 0.85). This calculation was made due to the low scientific evidence regarding the treatments used. For this purpose, the total number of visits to the center and those corresponding to said pathology were analyzed retrospectively. Overall, of the 2937 visits made, only 19 were for diagnosis of plantar wart and treatment, of which 12 were conservative and 7 were surgical. The formula to calculate the sample size was based on the Mann‐Whitney U for two independent samples.

$$n_1=\frac{w_1{\left(z_1-\frac{\alpha }{2}+z_1-\beta \right)}^2}{12w_1\left(1-w_1\right){\left(p_{x<y}-0,5\right)}^2}$$

where α is the level of significance, p _x<y and the probability that by taking an observation from each group at random the one from the reference group is lower, w ₁ the proportion of the sample in the reference group with respect to the total, and 1 − β the power of the statistical test to detect the desired differences. Table 1 shows the number of patients with each treatment necessary to achieve the minimum desired study power.

Table 1.

Results of the a priori sample size estimation.

	1 − β = 0.8	1 − β = 0.85
n1 (conservative)	37	42
n2 (surgical)	22	25

3. Results

The data of a total of 72 subjects was included, of which 33 (46%) were women, with an average age of 25. The youngest patient was 4 years old, and the oldest patient was 57.9 years old. The mean age was 17 years, and the average was 25 years. Of the 72 diagnosed lesions, the majority were located in the first ray and metatarsal heads (see Table 2). Approximately 30% of the lesions were treated surgically, and the rest were treated conservatively. Although the sample is not balanced, it met the criteria established in the preliminary study of sample size calculation.

Table 2.

Characteristics of the sample.

	Surgical treatment	Conservative treatment	Total
Cases (n, %)	28, 38%	44, 62%	72
Sex (n, % women)	19	14	33, 46%
Age (years)	17	41.3	24.8 (16.9) (4–58)
Foot (n left/n right)	28	44	39/33
Injury location (n, %)
First radio (n)	14	10	24, 33%
Metatarsal head (n)	6	17	23, 32%
Heel (n)	5	7	12, 17%
Toes (n)	1	9	10, 14%
Plantar vault (n)	2	1	2, 4%
Size (mm)	4.82	3.27	3.9 (1–9)

Overall, the size of the lesions ranged between 1 and 9 mm, with the average size being 3.9 (SD 1.6) mm. The treatment duration until the clinical resolution varied between 4 and 393 days, with a mean of 51.8 (SD 65.9) days. Specifically, Figure 2 shows a histogram comparing clinical resolution times according to the treatment performed, from which it can be deduced that surgical treatment times were shorter. The number of necessary sessions varied between 2 and 22, being less in the case of surgical treatment, since it was 4 (range 3–10) compared to 6.5 (range 2–22) for conservative treatment. Figure 3 shows a histogram comparing the number of cures according to treatment. 77.8% attended the control visit, and we were able to verify that everything was correct.

Figure 2.

Histograms representing total number of days of treatment vs. type of treatment.

Figure 3.

Number of cures vs. type of treatment.

3.1. Inferential Synthesis

A statistically significant association was found between the treatment time and the number of cures, with R ² = 0.332. Furthermore, a low relationship was found between the number of cures and the size of the lesion, with R ² = 0.064.

The surgical treatment time was significantly shorter than that of conservative treatments, which suggested the convenience of surgical treatment if treatment time is to be reduced (Figure 4). The log‐linear model for particular effects of each of the factor levels suggested an estimated average time of 14.8 days (intercept) in the same location. This indicated that performing a conservative treatment can last up to 2.5 times longer, which on a practical level implies 37.1 days on average to heal (Figure 5). On the other hand, injuries to the fingers take the longest to heal. Furthermore, when these are treated conservatively, the times increase by 1.9 compared to the surgical recovery time, which on a practical level means 21.9 days compared to 70.1 days.

Figure 4.

Treatment time according to type of treatment.

Figure 5.

Days of treatment, depending on type of treatment and location of the lesion.

4. Discussion

The comparison of the effectiveness of plantar wart excision vs. conservative treatments suggested that the surgical solution represents shorter recovery times. However, this is a treatment of choice, and the largest part of the study sample usually opted to perform topical and conservative treatments. Whether this was due to conservatism being the most commonly recommended by professionals [13] or to lack of knowledge of the evolution of surgery is up for speculation. Our findings (Figure 2) suggested favorable results of the evolution and healing times of plantar wart excision, as the first treatment option for a pathology that with conventional treatments presents recovery times between 12 weeks and 6 months [13].

As for the time spent on treatment, the results allow us to state that wart surgery required shorter times, with an average of 11.7 days before discharge. This parameter was longer in conservative solutions since the average time was an average of 73 days, regardless of parameters such as the patient's age, affected foot, sex, or lesion size. With respect to the literature consulted, the study of Saipoor et al. [19], for the surgical removal of plantar warts with a rotation skin flap, although it presented good results, it should be noted that the closure of the incisions was by first intention and the removal of the stitches was carried out after 3 weeks. Therefore, closure by secondary intention in our study presents better results for wart excision since our times are shorter.

As for conservative times, there is much more bibliography. For instance, the findings were consistent with the study of García‐Oreja et al. [20], who suggested a treatment length with bleomycin of 6–24 weeks. Regarding the treatment with nitric acid, our average healing time was longer than that published for the treatment of a mosaic plantar wart, which is not the type of plantar lesion that we addressed in the present study [20].

It should be noted that the lesions that make up the sample are within the normal range, with the smallest being 1 mm and the largest being 9 mm. In most studies, this variable is not reported [13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. Considering that the average of the lesions was 3.9 mm, patients with larger lesions were positioned in the choice of surgical treatment, on the other hand, patients with smaller lesions opted for performing conservative treatments.

In reference to the conservative treatments applied in the study sample, the treatment with nitric acid was given in a very small sample, but it is enough to show that the healing times are shorter than those of bleomycin, and the combination of nitric acid and bleomycin. There are no studies that compared the outcomes of both treatments, but the published treatments referring to the use of intralesional bleomycin do present healing times greater than 24 weeks and 13 weeks, respectively [18, 22]. Stating that intralesional treatment with bleomycin is the most effective compared to treatments with other intralesional procedures for warts, such as Candida antigen and Vitamin D3 [22].

Regarding the location of the lesion, we can affirm that surgery has been the most used treatment for lesions to the first ray. On the other hand, conservative treatment has been the most used for lesions to the metatarsal heads. It only refers to the discomfort that this type of lesion causes in patients in comparison with this lesion in another region or part of the body due to standing due to direct pressure. These lesions are more painful on the sole of the foot than, for example, on the hand [21, 22, 23]. We suspect that lesions to the first ray, being directly related to the last phase of gait, which needs the first ray for propulsion, cause continuous discomfort and that is why patients would rather undergo faster treatment, although this entails a few days of postsurgical recovery. As for patients with lesions to the metatarsal heads, it will depend on the support characteristics and morphology of the foot to know the load they support, which is probably the reason why most patients prefer to perform conservative treatment, although in this location, surgery can also be performed. Indeed, this was the second most frequent location after the first radius and presented a shorter recovery time.

Our study sample was classified by lesion location. We agreed with the study of Cintado et al. [25] that the lowest percentage of injuries appears in areas of non‐support, such as the plantar vault. There may be two justifications for this. The first is that, since contagion is more unlikely due to not having direct contact with contaminated surfaces or areas. Additionally, there is the possibility that the patient does not feel discomfort during his daily activity and, consequently, does not come to the consultation for treatment. However, it is true that we do not have data to make this statement, it is only speculation.

4.1. Limitations

The main limitation is the failure to consider the level of pain that the different treatments caused to the patients, since this parameter was not available in the database. Data analysis did not consider possible treatment complications, including infection, bleeding, or recurrence. Another limitation of the study is the lack of randomization due to the retrospective nature of the study. Retrospective designs based on clinical records could involve greater limitations than prospective, with possible biases related to risk factors, impact of events, or other measures. However, possible measures were taken to reduce the impact on the results and preserve the rigor of the data, with an entire data set that was systematically checked by the biometrician in charge of this study.

5. Conclusions

The excision of the plantar wart reduces the duration of the treatment by around 50% compared to conservative treatments analyzed in the study, such as nitric acid, bleomycin, and a combination of both. Therefore, surgical excision of the plantar wart could be considered a possible first treatment of choice, as it represents a short‐term and effective treatment compared to conservative therapies used in the podiatric field.

Future studies should be oriented to assess recurrences after both lines of treatment to confirm the findings ultimately.

The authors state that there is a need to carry out randomized controlled clinical trials that compare surgical treatment against other treatments, such as laser and/or cryotherapy, to obtain more specific results.

Author Contributions

María José Chiva Miralles: conceptualization, formal analysis, investigation, methodology, supervision, writing – original draft, writing – review and editing. Jose Maria Blasco Igual: conceptualization, formal analysis, investigation, methodology, supervision, writing – original draft, writing – review and editing. Cecili Macián Romero: conceptualization, supervision. Enrique Sanchis Sales: conceptualization, investigation, writing – review and editing. Carmen García Gomariz: conceptualization. Adrián Jorda Vallés: conceptualization.

Conflicts of Interest

The authors declare no conflicts of interest.

Transparancy Statement

María José Chiva Miralles affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.