Name: Local Hyperthermia for Warts Treatment (Video) | JoVE Journal
Uploaded: 2024-11-08T14:40:00.000+00:00
Duration: 4 min 25 s
Description: Learn local hyperthermia for wart treatment in dermatology using precise temperature protocols. This method offers high success rates with minimal side effects for HPV-related lesions.

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5 minutes

The authors have no acknowledgments.

Informed consent was obtained from all participants and the treatment protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.
1. Patient selection
<ol>
	<li>Use the following inclusion criteria to include patients who show a clear diagnosis of HPV infection in a common wart, plantar wart, or condyloma acuminatum; the product is indicated for patients who are capable of adhering to medical advice provided by their healthcare practitioners. Ensure that patients can comply with prescribed treatment regimens and adhere to medical directives during therapy to achieve optimal outcomes.
	<ol>
		<li>Pregnancy is not an absolute contraindication for treatment. Prior to therapy, disclose potential risks such as vaginal hemorrhage, spontaneous abortion, fetal demise, and congenital anomalies. Informed consent must be obtained after the patient understands these risks.</li>
	</ol>
	</li>
	<li>Use the following exclusion criteria: Do not apply therapeutic interventions directly to skin lesions in the periocular region. Avoid the management of skin lesions characterized by purulent infections. Do not treat patients who are characterized by a tendency for severe keloid or hypertrophic scar formation. Refrain from treating patients diagnosed with a significant impairment in blood coagulation mechanisms. Do not proceed with treatment for patients exhibiting a documented photosensitivity reaction specifically to red light wavelengths. Do not treat warts that are concomitant with localized skin tumors.</li>
</ol>
2. Target skin lesion selection
<ol>
	<li>For an individual skin lesion, adjust the angle and elevation as needed and apply targeted treatment directly to the lesion (Figure 1).</li>
	<li>For cases involving multiple lesions, select a lesion that is relatively big, planar, and suitable for perpendicular irradiation. The terminology target lesion refers to the lesion chosen for hyperthermia exposure, while lesions not selected for irradiation are referred to as non-target lesions.</li>
	<li>In order to safeguard the patient from potential harm or discomfort during the therapeutic process, avoid sensitive regions. This includes but is not limited to the periocular area. Careful attention to these areas is imperative to ensure patient safety and comfort throughout the treatment.</li>
	<li>Selection of new target points: In cases where the original target point has been resolved but other warts remain, use the criteria described above to select a new target lesion, ensuring consistency in the treatment approach.</li>
</ol>
3. Hyperthermia treatment
<ol>
	<li>Turn on the power switch. Ensure that the device is connected to a power source and flip the switch to the On position. After powering on, the display appears on the machine&#39;s operating screen. The machine allows for the treatment of one patient at a time, and the following are the specific steps for operation.</li>
	<li>Access the registration form: Navigate to the registration module within the machine&#39;s interface. Enter the patient&#39;s basic information by inputting the following details into the corresponding fields: name, gender, age, skin lesion location, skin lesion size, and number of skin lesions.</li>
	<li>The treatment head of this machine is equipped with an integrated camera, enabling photography by simply positioning the treatment head over the affected area. To capture an image of the lesion, click the Capture or Photo button on the screen.</li>
	<li>Level selection: The device offers a range of temperature settings and operational modes to cater to various therapeutic needs. Select from nine temperature levels, starting at 40 &#176;C on Level 1 and increasing to 46 &#176;C on Level 9 (Figure 2A).</li>
	<li>Mode selection: Choose the appropriate treatment mode from the options provided by the machine based on the patient&#39;s condition and treatment plan (Figure 2B).The standard protocol suggests starting at level 5, mode two, but it is essential to adjust the temperature based on the patient&#39;s feedback. 
	NOTE: If a patient experiences a mild, tolerable sensation akin to pinpricks, the treatment may proceed. However, if intense discomfort is felt before reaching the designated temperature, the level should be promptly reduced to prevent injuries such as burns and blisters. On the other hand, if the patient perceives only tolerable, intermittent stinging at the set temperature, it is safe to continue with the treatment.
	<ol>
		<li>Mode one: This mode increments the temperature by 1 &#176;C every 3 min, with each pulse lasting for 10 s.</li>
		<li>Mode two: This is similar to mode one, but each pulse lasts for 20 s, providing a longer exposure to the increased temperature.</li>
		<li>Mode three: This mode accelerates the temperature rise to 2 &#176;C per pulse, with each pulse sustained for 20 s, maintaining a consistent 3 min interval between pulses.</li>
		<li>To initiate the treatment, configure the device settings to Mode two at Level 5 (which corresponds to a temperature of 43 &#176;C). This configuration has been established12,13 as the optimal starting point for patient therapy, ensuring a balance between efficacy and patient comfort. The appropriate treatment level can vary significantly among individuals, with the patient&#39;s tolerance playing a crucial role in its determination.</li>
	</ol>
	</li>
	<li>Set the treatment duration: To ensure optimal treatment efficacy, set the irradiation duration to a minimum of 30 min for each session. This recommended time frame is crucial for achieving the desired therapeutic outcomes.</li>
	<li>Assist the patient in positioning properly. Guide the patient to a comfortable and stable position that allows for effective treatment without discomfort.</li>
	<li>Manually adjust the mechanical arm coarsely. Use manual controls to position the mechanical arm roughly over the treatment area, ensuring it is in the correct general vicinity. 
	NOTE: The treatment device is designed for ease of use, requiring only that the treatment head be oriented generally towards the vicinity of the lesion. For instance, if the skin lesion is located on the hand, the treatment head should be gently positioned near the general area of the lesion on the hand, followed by precise adjustments for accurate targeting.</li>
	<li>Fine-tune the mechanical arm using the cross switch. Maintain a standard distance of 5 cm between the device head and the lesion.
	<ol>
		<li>The machine is equipped with a cross switch that facilitates the adjustment of the mechanical arm connected to the irradiation head. Initially, the irradiation head emits two light beams at a specific angle, resulting in two separate light spots. Manipulate the cross-switch and these two light spots will gradually merge into a single, circular spot. Once the spots have converged into a single, round point, this indicates that the distance is optimal, and irradiation can begin.</li>
	</ol>
	</li>
	<li>Initiate the irradiation process. Once the mechanical arm is correctly positioned, click the Start button to begin the treatment session.</li>
	<li>Treatment monitoring: During treatment, assess the patient&#39;s comfort every 2-3 min and adjust treatment intensity accordingly.If intolerance is noted, promptly lower the intensity to prevent blisters. Ask the patients to use the bedside call bell for any discomfort; staff should respond swiftly to address needs and ensure safety. 
	NOTE: To guarantee that the temperature reaches the designated set point without surpassing it, the light source&#39;s emission head is equipped with an integrated temperature sensor. This sensor continuously monitors the temperature, compares it with the preset value, and automatically adjusts the output to keep the treatment temperature close to the set point without exceeding it. Additionally, the real-time temperature is displayed promptly on the screen. To ensure optimal treatment outcomes, it is crucial to conduct frequent checks of the light spot position and the distance of the device emission window from the warts.
	<ol>
		<li>In the event of patient movement that affects the treatment focus, the device is designed to automatically trigger an alarm. Upon the alarm, staff should promptly attend to the patient to assist with repositioning without the need to manually pause the treatment. The device will pause automatically upon the alarm trigger.</li>
		<li>Once the patient has been repositioned and the device has successfully reestablished focus, the treatment will automatically continue without manual intervention, ensuring minimal disruption to the therapeutic process.</li>
	</ol>
	</li>
	<li>Treatment termination: The remaining time will be continuously displayed during the treatment process. Upon reaching the set duration, the device&#39;s control panel will automatically revert to the main interface, signaling the end of the treatment. After treatment, reset the mechanical arm to its original position. Ensure it is fully retracted and ready for the next session or storage. Inform the patient of their next treatment appointment.</li>
</ol>
4. Treatment plan
<ol>
	<li>The specific therapeutic protocol is illustrated in Figure 3. Typically, the initial treatment period lasts for 15 &#177; 3 days, during which target and non-target lesions exhibit no particularly significant changes. Ensure that the treatment period is approximately 15 days, with a permissible variation of &#177; 3 days.</li>
	<li>After a 2-week initial phase, commence the intensive treatment phase, with treatments administered once weekly for a total of 10 consecutive weeks. Following this, continue with treatments at the same frequency until clear changes in non-target lesions are observed. Subsequently, reduce treatments to once a month or once every two months until the non-target lesions show noticeable changes, such as the disappearance of some warts, the appearance of characteristic apoptotic necrotic spots in the center of warts, or a significant reduction in wart size, indicating remission.</li>
	<li>Monitor the non-target lesions for significant changes, including partial regression of warts, the emergence of characteristic apoptotic necrotic black spots at the lesion centers, and a notable decrease in wart size. Once these changes are observed, adjust the treatment frequency to once every 1-2 months until full recovery is achieved.</li>
	<li>Following an initial period of 2-3 min to assess the patient&#39;s tolerance, adjust the treatment intensity in accordance with the observed response.</li>
</ol>
5. Precautions
<ol>
	<li>In cases where the patient exhibits hypersensitivity to the initial short-term exposure, immediately reduce the treatment intensity to minimize the risk of blistering.</li>
	<li>Keep each treatment session at 30 min, ensuring consistent perpendicular irradiation directed at the target lesion throughout the entire duration.</li>
	<li>To ensure the induction of an immune response, predicate the choice of modality and intensity on the patient perceiving a mild pricking sensation.</li>
	<li>If a blister does form, manage it appropriately and resume treatment once the blisters have fully resolved.</li>
	<li>The application of hyperthermia is contraindicated for skin areas with open wounds.</li>
	<li>Start with hyperthermia, and if necessary, provide medication treatment. If the initial therapeutic outcome is unsatisfactory, augment local hyperthermia with additional treatments, including topical antiviral medications like imiquimod. This combination may improve cure rates and may reduce the treatment duration for topical medications.</li>
	<li>Ensure the selection of warts for hyperthermia treatment targets areas that are relatively flat and facilitate perpendicular irradiation.</li>
</ol>

Effective Wart Treatment with Local Hyperthermia: A Minimally Invasive Approach

<ol><li>White, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Manipulation+of+epithelial+differentiation+by+HPV+oncoproteins%5BTitle%5D)+AND+%22Viruses%22%5BJournal%5D)">Manipulation of epithelial differentiation by HPV oncoproteins.</a> Viruses. 11 (4), 369(2019).</li>
<li>Witchey, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Plantar+warts%3A+Epidemiology%2C+pathophysiology%2C+and+clinical+management%5BTitle%5D)+AND+%22J+Osteo+Med%22%5BJournal%5D)">Plantar warts: Epidemiology, pathophysiology, and clinical management.</a> J Osteo Med. 118 (2), 92-105 (2018).</li>
<li>Burli, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((HPV+vaccination+status+and+resolution+of+warts+in+pediatric+patients%5BTitle%5D)+AND+%22Indian+J+Dermatol%22%5BJournal%5D)">HPV vaccination status and resolution of warts in pediatric patients.</a> Indian J Dermatol. 66 (6), 604-608 (2021).</li>
<li>Lofty, A. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Intralesional+combined+furosemide+and+digoxin+in+cutaneous+warts+treatment%3A+A+randomized+controlled+clinical+trial%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">Intralesional combined furosemide and digoxin in cutaneous warts treatment: A randomized controlled clinical trial.</a> Derma Ther. 35 (12), e15935(2022).</li>
<li>García-Oreja, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Topical+treatment+for+plantar+warts%3A+A+systematic+review%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">Topical treatment for plantar warts: A systematic review.</a> Derma Ther. 34 (1), e14621(2021).</li>
<li>Fields, J. R., Saikaly, S. K., Schoch, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Intralesional+immunotherapy+for+pediatric+warts%3A+A+review%5BTitle%5D)+AND+%22Pedia+Derma%22%5BJournal%5D)">Intralesional immunotherapy for pediatric warts: A review.</a> Pedia Derma. 37 (2), 265-271 (2020).</li>
<li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Amplifying+cancer+treatment%3A+advances+in+tumor+immunotherapy+and+nanoparticle-based+hyperthermia%5BTitle%5D)+AND+%22Front+Immunol%22%5BJournal%5D)">Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia.</a> Front Immunol. 14, 1258786(2023).</li>
<li>Chen, J. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Successful+treatment+of+extensive+flat+warts+with+local+hyperthermia%3A+A+case+report%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">Successful treatment of extensive flat warts with local hyperthermia: A case report.</a> Derma Ther. 33 (6), e14525(2020).</li>
<li>De Planell-Mas, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Human+papillomaviruses+genotyping+in+plantar+warts%5BTitle%5D)+AND+%22J+Med+Virol%22%5BJournal%5D)">Human papillomaviruses genotyping in plantar warts.</a> J Med Virol. 4689 (5), 902-907 (2017).</li>
<li>Li, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Local+hyperthermia+could+induce+migrational+maturation+of+Langerhans+cells+in+condyloma+acuminatum%5BTitle%5D)+AND+%22J+Dermatol+Sci%22%5BJournal%5D)">Local hyperthermia could induce migrational maturation of Langerhans cells in condyloma acuminatum.</a> J Dermatol Sci. 54, 121-123 (2009).</li>
<li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia%3A+a+pilot+report%5BTitle%5D)+AND+%22Dermatol+Ther%22%5BJournal%5D)">Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.</a> Dermatol Ther. 27, 109-112 (2014).</li>
<li>Hildebrandt, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+cellular+and+molecular+basis+of+hyperthermia%5BTitle%5D)+AND+%22Crit+Rev+Oncol+Hematol%22%5BJournal%5D)">The cellular and molecular basis of hyperthermia.</a> Crit Rev Oncol Hematol. 43, 33-56 (2002).</li>
<li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Local+hyperthermia+at+44+%C2%B0C+for+the+treatment+of+plantar+warts%3A+a+randomized%2C+patient-blinded%2C+placebo-controlled+trial%5BTitle%5D)+AND+%22J+Infect+Dis%22%5BJournal%5D)">Local hyperthermia at 44 °C for the treatment of plantar warts: a randomized, patient-blinded, placebo-controlled trial.</a> J Infect Dis. 201 (8), 1169-1172 (2010).</li>
<li>Chen, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clinical+observation+and+study+of+local+hyperthermia+for+treating+plantar+warts%3A+A+pilot+study+with+38+patients%5BTitle%5D)+AND+%22Front+Medi%22%5BJournal%5D)">Clinical observation and study of local hyperthermia for treating plantar warts: A pilot study with 38 patients.</a> Front Medi. 10, 1087659(2023).</li>
<li>Qi, R. Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clearance+of+multiple+cutaneous+warts+by+targeting+a+single+lesion%3A+A+randomized+comparative+evaluation+of+mild+local+hyperthermia+versus+cryotherapy%5BTitle%5D)+AND+%22J+Am+Acad+Dermatol%22%5BJournal%5D)">Clearance of multiple cutaneous warts by targeting a single lesion: A randomized comparative evaluation of mild local hyperthermia versus cryotherapy.</a> J Am Acad Dermatol. 87 (6), 1443-1445 (2022).</li>
<li>Garcia-Oreja, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Topical+treatment+for+plantar+warts%3A+a+systematic+review%5BTitle%5D)+AND+%22Dermatol+Ther%22%5BJournal%5D)">Topical treatment for plantar warts: a systematic review.</a> Dermatol Ther. 34, e14621(2021).</li>
<li>Lipke, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+armamentarium+of+wart+treatments%5BTitle%5D)+AND+%22Clin+Med+Res%22%5BJournal%5D)">An armamentarium of wart treatments.</a> Clin Med Res. 4 (4), 273-293 (2006).</li>
<li>Forcier, M., Musacchio, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+overview+of+human+papillomavirus+infection+for+the+dermatologist%3A+disease%2C+diagnosis%2C+management%2C+and+prevention%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">An overview of human papillomavirus infection for the dermatologist: disease, diagnosis, management, and prevention.</a> Derma Ther. 23 (5), 458-476 (2010).</li>
<li>Stern, P., Levine, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Controlled+localized+heat+therapy+in+cutaneous+warts%5BTitle%5D)+AND+%22Arch+Dermatol%22%5BJournal%5D)">Controlled localized heat therapy in cutaneous warts.</a> Arch Dermatol. 128 (7), 945-948 (1992).</li>
<li>Pfau, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Nd%3AYAG+laser+hyperthermia+in+the+treatment+of+recalcitrant+verrucae+vulgares+%28Regensburg%27s+technique%29%5BTitle%5D)+AND+%22Acta+Dermato-Venereologica%22%5BJournal%5D)">Nd:YAG laser hyperthermia in the treatment of recalcitrant verrucae vulgares (Regensburg's technique).</a> Acta Dermato-Venereologica. 74 (3), 212-214 (1994).</li>
<li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Local+hyperthermia+versus+cryotherapy+for+treatment+of+plantar+warts%3A+A+prospective+multi-centre+non-randomized+concurrent+controlled+clinical+trial%5BTitle%5D)+AND+%22Acta+Dermato-Venereologica%22%5BJournal%5D)">Local hyperthermia versus cryotherapy for treatment of plantar warts: A prospective multi-centre non-randomized concurrent controlled clinical trial.</a> Acta Dermato-Venereologica. 102, adv00655(2022).</li>
<li>Yoshioka, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Suppression+of+contact+sensitivity+by+local+hyperthermia+treatment+due+to+reduced+Langerhans+cell+population+in+mice%5BTitle%5D)+AND+%22British+J+Dermatol%22%5BJournal%5D)">Suppression of contact sensitivity by local hyperthermia treatment due to reduced Langerhans cell population in mice.</a> British J Dermatol. 120 (4), 493-501 (1989).</li>
<li>Jiang, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Successful+treatment+of+periungual+warts+with+local+hyperthermia%3A+report+of+two+cases%5BTitle%5D)+AND+%22J+Dermatolog+Treat%22%5BJournal%5D)">Successful treatment of periungual warts with local hyperthermia: report of two cases.</a> J Dermatolog Treat. 33 (4), 2380-2382 (2022).</li>
<li>Huo, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia%3A+a+pilot+report%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.</a> Derma Ther. 27 (2), 109-112 (2014).</li>
<li>Zhao, S. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+multicenter+realworld+observation+to+evaluate+the+efficacy+of+cryotherapy+versus+local+hyperthermia+for+the+treatment+of+plane+warts%5BTitle%5D)+AND+%22Derma+Ther%22%5BJournal%5D)">A multicenter realworld observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.</a> Derma Ther. 35 (5), e15403(2022).</li>
</ol>

The authors have no conflicts of interest to declare.

Plantar warts, condylomata acuminata, and common warts all include mucocutaneous manifestations resulting from human papillomavirus (HPV) infection; these lesions can present as solitary skin lesions or, more commonly, as multiple lesions17.
In the continuous effort to manage warts induced by Human Papillomavirus (HPV), a diverse array of therapeutic strategies has been implemented. These include destructive methods, virucidal agents, antimitotic compounds, and immunotherapeutic approaches. Despite their varying degrees of success when used in isolation or in combination, these treatments are frequently associated with adverse effects such as pain, bleeding, secondary infections, and ulceration, underscoring the need for less invasive and more effective treatment options18.
The advent of hyperthermia has introduced a promising alternative to the current therapeutic landscape. Since its initial proposal in 1992, hyperthermia has been extensively researched and repeatedly shown to be effective in the treatment of warts19. Notably, a comparative analysis performed 4 months after the commencement of treatment revealed that 54.5% of patients treated with hyperthermia achieved complete clearance of their lesions. This outcome significantly surpassed the 27.2% clearance rate observed in the cryotherapy group in a study that included 35 participants15.
Temperature emerges as a pivotal factor in the efficacy of hyperthermia treatments for HPV-induced warts, with varying temperatures potentially leading to diverse therapeutic outcomes20. A study has indicated that the application of local hyperthermia at 44 &#176;C to a single lesion could result in the concurrent resolution of untreated plantar warts in 59.1% of the patients, underscoring the treatment&#39;s systemic effects21. However, reported cure rates for hyperthermia show considerable heterogeneity across studies.
The maximum tolerable thermal treatment temperature is 46 &#176;C. This is based on preliminary clinical observations, which indicate that temperatures exceeding 46 &#176;C can lead to skin injuries such as blisters and bullae.
Consequently, identifying the optimal therapeutic temperature has consistently been a focal point of research efforts. The reported efficacies in these previous studies correspond to the rates of therapeutic success observed in our clinical observations, suggesting consistency across different research settings13,14,15. A comparative analysis conducted months post-treatment revealed no significant difference in the clearance rates of targeted lesions between hyperthermia and cryotherapy, as reported by Qi et al.15. However, a significant advantage for hyperthermia was observed in the clearance of non-target lesions compared to cryotherapy15. In addition to its superior efficacy in clearing non-target lesions, hyperthermia was also associated with reduced pain during treatment. Patients who underwent cryotherapy experienced significantly higher pain scores on a visual analog scale (VAS) than those treated with hyperthermia, a difference that was statistically significant15.In a 3 month study by Wei et al., hyperthermia showed a significantly higher cure rate than placebo-controlled group13. Moreover, Chen&#39;s recent research noted no lesion recurrence in clinically cured patients upon final follow-up, suggesting hyperthermia&#39;s potential to reduce recurrence rates14.
To prevent blister occurrences, it is important to understand the conditions that may lead to blistering. In a study by Qi et al., it was observed that 2 out of 44 patients developed blisters15. Blisters were found to be more likely to form when the light was concentrated on very small warts, leading to direct exposure of the healthy skin surface or in patients with a heightened sensitivity to light. Thus, it is suggested to opt for thermal therapy on larger lesions, as smaller ones, such as filiform warts, might not be appropriate for this treatment approach13,15.
Extensive research has been dedicated to understanding the therapeutic mechanisms of hyperthermia in clearing warts. Hyperthermia&#39;s effectiveness is particularly notable due to its dual role: it induces specific immune responses against HPV-infected lesions, which are essential for both self-regression and treatment-assisted clearance of warts, and it also leads to relief in both target irradiated and non-irradiated skin lesions13,15. This targeted approach not only addresses the treated lesion but also has systemic implications; the immune reaction initiated by treating a single lesion can extend to untargeted or distant lesions. This broader effect is attributed to the systemic immune response elicited by the localized application of hyperthermia. As a result, lesions that have not been directly treated may also experience regression or achieve complete resolution, underscoring the potential of hyperthermia to offer comprehensive treatment for multiple warts13,15,18.
We observed that patients with multiple warts can also experience nearly simultaneous clearance of both targeted and non-targeted warts. This observation implies that hyperthermia potentially enhances the specific immune response against warts, highlighting its indirect but supportive role in immunotherapy. It appears to engage the skin&#39;s inherent mechanisms for the autonomous clearance of HPV infections. The principal mechanism underlying this efficacy is believed to be the modulation of Langerhans cell function within the specific immune response. This modulation enhances the ability to target and eliminate virus-infected keratinocytes13,15.
This also elucidates the rationale behind the relatively slower therapeutic onset observed with the therapy, as it may require time for the immune system to mount an effective response against the viral infection. The general application of hyperthermic therapy typically necessitates a duration of over months. Moreover, it is essential that the therapeutic phase and the intensified treatment phase are separated by a 2 week interval21,22. This protocol is based on the understanding that the homeostatic balance of Langerhans cells (LCs) within the epidermis is typically achieved within a one- to two-week timeframe. Yoshioka&#39;s research indicates that local hyperthermia at 43&#176;C restores LC homeostasis in the epidermis within 14 days22. This timing is crucial as LCs drive the immune response against HPV-infected keratinocytes. A 2 week treatment gap ensures an ample LC presence for the next treatment cycle. With a normal skin turnover of 52-75 days, a 3 month study endpoint suffices to assess both epidermal recovery and wart clearance, which are immune response-dependent13.
Compliance is a critical factor in ensuring the efficacy of thermotherapy treatments. At the initiation of therapy, patients are informed that the therapeutic effects, while gradual, are accompanied by markedly reduced pain sensation compared to conventional laser therapy, and there is an absence of risks such as bleeding. The treatment protocol is presented to patients, detailing the benefits and drawbacks, allowing them to make an informed decision about their ability to cooperate with the treatment plan. Consequently, patients who opt for thermotherapy are typically able to adhere to the treatment regimen, as they have a realistic psychological expectation of the treatment&#39;s progression. Furthermore, for patients with multiple comorbidities who express a fear of pain, a comprehensive explanation of the treatment&#39;s merits and demerits often results in willing engagement after they have grasped the potential benefits. Therefore, pre-treatment consultation and ongoing follow-up are deemed essential components of the therapeutic process.
Despite the variety of treatments for warts, there is a clear need for safer, more effective, and minimally invasive options that also minimize pain23. This is especially important for particular groups: patients with multiple warts, those with warts in sensitive areas like the genitalia and rectum, pregnant women, children who are sensitive to pain, individuals with serious systemic diseases, and patients with extensive condylomas who have had recurrences after standard treatments. This strategy involves personalized communication with these patients prior to treatment to address their specific needs and concerns. Despite the limitations associated with treatment options during pregnancy, many women with this condition experience progressive enlargement of verrucae. Local hyperthermia, proposed as a viable therapeutic approach for pregnant women, merits consideration as a safer alternative due to its favorable safety profile in treatment24.
In conclusion, the current study&#39;s findings highlight the efficacy and safety of local hyperthermia as an innovative therapeutic strategy for treating warts, suggesting its potential as a viable alternative to traditional treatments25. Although the precise mechanisms and optimal conditions for local hyperthermia are not fully understood, this treatment has shown promising efficacy and safety in wart management. However, further analysis with larger clinical samples is needed to delineate the differences between local hyperthermia and conventional therapies more clearly. Future studies should encompass larger clinical trials to validate our findings and assess the impact of variables like wart size and the efficacy of previous treatments on wart resolution.

Warts, which are benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the stratum corneum of the skin1. They are most commonly manifested clinically as the formation of warts, including plantar warts, genital warts, and common warts2. Warts are typically benign in nature, and although they are occasionally subject to spontaneous resolution3, a considerable number of individuals prefer to have them excised primarily due to the discomfort they cause or social embarrassment4.
A variety of therapeutic approaches have been employed to treat warts, including laser therapy, antiviral treatments, antimitotic medications, and immunotherapies5. However, these treatments are often accompanied by adverse effects such as pain, bleeding, secondary infections, and ulceration6. Consequently, there exists an urgent demand for treatment modalities that offer enhanced safety, efficacy, and minimal invasiveness, particularly for special populations, including the elderly, children, and pregnant women, as well as for specific anatomic sites such as the perianal region and the vulva. 
Addressing the demand for effective and minimally invasive treatments, local hyperthermia has emerged as a promising therapeutic strategy. Hyperthermia has been effectively utilized in the treatment of certain neoplasms7, and there are numerous studies that have demonstrated the efficacy of localized hyperthermia in the management of warts, yielding highly satisfactory outcomes8,9. The hyperthermia device used here offers a range of customizable settings, including adjustable levels and modes, designed to meet diverse therapeutic needs. The overall goal of this hyperthermia device is to provide a non-invasive, safe, and efficacious approach for wart management that is suitable for a wide range of patient populations, including those who are not candidates for more invasive procedures. 
This technique of using local hyperthermia for HPV-related warts is positioned within a growing body of literature that explores the role of heat in modulating immune cell function. It builds on a previous study that established the importance of Langerhans cells in the immune response to skin infections and how their balance can be restored through controlled heat application10.
Individuals with diagnosed HPV-related warts, such as common, plantar, or genital, and who are compliant with medical guidance are considered appropriate candidates for local hyperthermia treatment. Although pregnancy is not an absolute contraindication, pregnant patients must be made aware of the associated risks and must provide informed consent to proceed11. This treatment is not recommended for those with periocular lesions, purulent infections, a propensity for severe scarring, coagulation disorders, or known photosensitivity. Additionally, patients with warts in proximity to tumors are not candidates, as this could suggest an underlying neoplastic process.

<table><tbody><tr><td>YY-WRY-V02 infrared specific wave photothermal therapeutic instrument</td><td>Liaoning Yanyang Medical Equipment Co., Ltd</td><td>No. ZL200720185403.3, China Medical University, China)</td><td></td></tr></tbody></table>

local hyperthermia for warts treatment

Local Hyperthermia for Warts Treatment

Warts, benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the stratum corneum of the skin. The development of warts is the most common clinical manifestation of HPV, with plantar warts, condylomata acuminata, and common warts being the most frequently observed types. These growths can be unsightly and sometimes painful, affecting the quality of life for those afflicted. Although various treatments are available, ranging from topical medications to surgical procedures, the quest for a treatment that is both safe and effective while minimizing invasiveness continues. This is particularly crucial for populations with heightened risk factors, such as immuno-compromised individuals. In the clinical need for minimally invasive treatments, local hyperthermia has emerged as a promising therapeutic strategy for wart management. As demonstrated in various studies, local hyperthermia is effective as a standalone treatment, offering a valuable alternative for patients seeking less intrusive therapeutic options.

Multiple hospitals have contributed to a series of investigations into the therapeutic effects of hyperthermia. This research encompasses single-arm clinical observational studies, placebo-controlled trials, and comparative analyses with cryotherapy, with the findings being published in various articles13,14,15. They found that hyperthermia was also associated with reduced pain during treatment had comparable therapeutic effects to conventional treatment, and even superior efficacy in some cases13,14. Notably, not only did the target lesions at the irradiated sites regress but there was also a significant regression of non-target lesions at non-irradiated sites. Moreover, compared to conventional treatment, there was a marked reduction in pain levels15, which may potentially enhance patient compliance and overall treatment experience.
Our study indicated that hyperthermia treatment resulted in the complete resolution of plantar warts in 13 out of 21 patients (59.1%), with partial remission observed in 8 (38.1%)14. The primary adverse event during the procedure was a mild burning sensation, with minimal observation of other side effects. Bullae formation was noted in two patients at the treatment sites. The demographics and clinical characteristics of the 21 patients who achieved resolution are detailed in Table 1. Additionally, there was no recurrence of lesions in the 13 clinically cured patients upon follow-up. These findings are juxtaposed with the average cure rates from a comprehensive review16,in the study, a variety of treatment modalities were investigated, including Imiquimod 5% cream, laser surgery, cryotherapy, surgical removal, and placebo or no treatment. Our research indicates that the efficacy of our method is comparable to that of Imiquimod 5% cream, laser surgery, surgical removal, and placebo or no treatment, but it is inferior to the efficacy of cryotherapy. Although hyperthermia's cure rates are not superior to those of conventional treatments, it is noteworthy for its minimally invasive nature, causing less pain and tissue damage.
Moreover, our study particularly emphasizes the low recurrence rate associated with hyperthermia; there was no recurrence of lesions in the 13 clinically cured patients at the last follow-up. It is particularly noteworthy that hyperthermia treatment exhibited salutary effects on both targeted and non-targeted skin lesions in individuals presenting with extensive cutaneous warts. This observation underscores the potential of hyperthermia to confer a systemic therapeutic benefit, promoting the regression of not only the lesions that were directly subjected to treatment but also those that were anatomically distinct and untreated14.
Our clinical observations demonstrate that hyperthermia treatment led to marked improvements across all types of warts, regardless of their location or the number of lesions present (Figure 4). Figure 4A depicts the appearance of plantar warts before the initiation of treatment. In contrast, Figure 4B illustrates the complete remission observed one month after the application of local hyperthermia. Figure 4C, D showcases the transformation of vulvar condylomata acuminata from the pre-treatment state to the post-treatment state, with a full resolution of the skin lesions achieved 1 month after commencing the therapy. Figure 4E,F depict penile condylomata acuminata in the pre-treatment state, and Figure 4G,H show the lesions' complete regression after 1 month. In a patient with extensive anogenital warts affecting both genital and perianal regions, with a focus on genital warts as the primary treatment area (Figure 4I), initial results after 1 month (Figure 4J) showed no significant improvement in skin lesions, accompanied by the development of erythema at the target sites. However, after 2 months of treatment (Figure 4K), there was a noticeable reduction in warts in both perianal and vulvar areas despite persistent erythema. By the end of the 3-month treatment period (Figure 4L), all warts had resolved completely, and the erythema induced by hyperthermia at the treatment sites had subsided. Notably, they reveal the intriguing phenomenon of concurrent clearance of both targeted and non-targeted lesions, including the spontaneous healing of untreated perianal lesions in a complex genital case.
<img alt="Laser therapy setup on foot, red light used for medical treatment analysis." class="xfigimg" src="/files/ftp_upload/67384/67384fig1.jpg" data-altupdatedat="1788304762000" data-alt="Figure 1"> 
Figure 1: Irradiation of lesion. Adjust the angle for the plantar warts and begin irradiation once the hyperthermia device is activated. <a href="https://www.jove.com/files/ftp_upload/67384/67384fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Temperature control bar graph; level vs. degree Celsius. Cooling modes table describes pulses." class="xfigimg" src="/files/ftp_upload/67384/67384fig2.jpg" data-altupdatedat="1788304762000" data-alt="Figure 2"> 
Figure 2: Temperature settings and operational modes for thermotherapy device. (A) The machine offers nine adjustable temperature levels, each corresponding to a specific temperature setting as follows: Level 1: 40 °C; Level 2: 40.8 °C; Level 3: 41.5 °C; Level 4: 42.3 °C; Level 5: 43 °C; Level 6: 43.8 °C; Level 7: 44.5 °C; Level 8: 45.3 °C; Level 9: 46.0 °C. (B) The device has three modes for customizable temperature and exposure time adjustments. <a href="https://www.jove.com/files/ftp_upload/67384/67384fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Treatment timeline diagram; phases: treatment, intensive treatment, therapeutic observation." class="xfigimg" src="/files/ftp_upload/67384/67384fig3.jpg" data-altupdatedat="1788304762000" data-alt="Figure 3"> 
Figure 3: Local hyperthermia treatment. The treatment plan consists of three phases: the primary treatment phase, the intensified phase, and the observation phase. <a href="https://www.jove.com/files/ftp_upload/67384/67384fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Medical imagery of dermatological and genital conditions; close-ups for clinical examination." class="xfigimg" src="/files/ftp_upload/67384/67384fig4.jpg" data-altupdatedat="1788304762000" data-alt="Figure 4"> 
Figure 4: Before and after local hyperthermia treatment comparison. (A) Plantar warts before treatment. (B) One month after treatment with local hyperthermia (complete remission). (C) Vulvar condylomata acuminata before treatment. (D) The skin lesions completely resolved after 1 month of treatment. (E, F) Penile condylomata acuminata before treatment. (G, H) The skin lesions completely resolved after 1 month of treatment. (I) The patient presented with extensive condylomata acuminata affecting the genital and perianal regions, with genital warts designated as the primary target area for treatment. (J) After 1 month of treatment, there was no significant improvement in the skin lesions, and erythema developed at the target sites. (K) After 2 months of treatment, although erythema at the treatment sites persisted, warts in both the perianal and vulvar areas showed significant reduction. (L) After 3 months of treatment, the multiple warts achieved complete clearance, and the reactive erythema to the hyperthermia at the irradiated sites subsided. <a href="https://www.jove.com/files/ftp_upload/67384/67384fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Variable</td>
			<td>Response group (n=21)</td>
		</tr>
		<tr>
			<td>Age median (QS)</td>
			<td>32 years (26.5, 43.5)</td>
		</tr>
		<tr>
			<td>Gender (Male/%)</td>
			<td>11/52.4%</td>
		</tr>
		<tr>
			<td>Duration median (QS)</td>
			<td>12 (3,24)</td>
		</tr>
		<tr>
			<td>Number median (QS)</td>
			<td>5 (1,26.5)</td>
		</tr>
		<tr>
			<td>Diameter median (QS)</td>
			<td>8 mm (4,15)</td>
		</tr>
		<tr>
			<td>Average follow-up time</td>
			<td>4.6 months</td>
		</tr>
		<tr>
			<td>Remission (yes/%)</td>
			<td>8/38.1%</td>
		</tr>
		<tr>
			<td>Previous treatment(yes/%)</td>
			<td>9/42.9%</td>
		</tr>
	</tbody>
</table>
Table 1: Demographics and clinical characteristics of patients (N=21). This table has been modified from14.

Here, we present a protocol for local hyperthermia, a new and effective therapeutic for treating warts. We also showcase its safety and efficacy as an independent treatment.

Warts, benign epidermal proliferations, are a direct result of human papillomavirus (HPV) infection, specifically targeting the keratinocytes within the ...

Research

JoVE Journal

Behavior

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Local Hyperthermia for Warts Treatment

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