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

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	<li>White, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Manipulation+of+epithelial+differentiation+by+HPV+oncoproteins.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Plantar+warts:+Epidemiology,+pathophysiology,+and+clinical+management.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HPV+vaccination+status+and+resolution+of+warts+in+pediatric+patients.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intralesional+combined+furosemide+and+digoxin+in+cutaneous+warts+treatment:+A+randomized+controlled+clinical+trial.">Intralesional combined furosemide and digoxin in cutaneous warts treatment: A randomized controlled clinical trial.</a> Derma Ther. 35 (12), e15935 (2022).</li><li>Garc&#237;a-Oreja, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+treatment+for+plantar+warts:+A+systematic+review.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intralesional+immunotherapy+for+pediatric+warts:+A+review.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amplifying+cancer+treatment:+advances+in+tumor+immunotherapy+and+nanoparticle-based+hyperthermia.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+treatment+of+extensive+flat+warts+with+local+hyperthermia:+A+case+report.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+papillomaviruses+genotyping+in+plantar+warts.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+could+induce+migrational+maturation+of+Langerhans+cells+in+condyloma+acuminatum.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia:+a+pilot+report.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+cellular+and+molecular+basis+of+hyperthermia.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+at+44+&#176;C+for+the+treatment+of+plantar+warts:+a+randomized,+patient-blinded,+placebo-controlled+trial.">Local hyperthermia at 44 &#176;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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+observation+and+study+of+local+hyperthermia+for+treating+plantar+warts:+A+pilot+study+with+38+patients.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+multiple+cutaneous+warts+by+targeting+a+single+lesion:+A+randomized+comparative+evaluation+of+mild+local+hyperthermia+versus+cryotherapy.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+treatment+for+plantar+warts:+a+systematic+review.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+armamentarium+of+wart+treatments.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+of+human+papillomavirus+infection+for+the+dermatologist:+disease,+diagnosis,+management,+and+prevention.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+localized+heat+therapy+in+cutaneous+warts.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nd:YAG+laser+hyperthermia+in+the+treatment+of+recalcitrant+verrucae+vulgares+(Regensburg's+technique).">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+hyperthermia+versus+cryotherapy+for+treatment+of+plantar+warts:+A+prospective+multi-centre+non-randomized+concurrent+controlled+clinical+trial.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Suppression+of+contact+sensitivity+by+local+hyperthermia+treatment+due+to+reduced+Langerhans+cell+population+in+mice.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+treatment+of+periungual+warts+with+local+hyperthermia:+report+of+two+cases.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clearance+of+genital+warts+in+pregnant+women+by+mild+local+hyperthermia:+a+pilot+report.">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/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+multicenter+realworld+observation+to+evaluate+the+efficacy+of+cryotherapy+versus+local+hyperthermia+for+the+treatment+of+plane+warts.">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 immunoth...

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

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 h...

Author Spotlight: Dermatopathology and the Treatment of Sexually Transmitted Diseases

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.

Local Hyperthermia for Warts Treatment

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

Research

JoVE Journal

Behavior

1.5K Views.  The First Affiliated Hospital of Chongqing Medical University. 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.

Video: Author Spotlight: Dermatopathology and the Treatment of Sexually Transmitted Diseases

Thermal Ablation for the Treatment of Abdominal Tumors

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ablation procedure, a thin applicator is guided into the target tumor under imaging guidance. Energy is then applied to the tissue until temperatures rise to cytotoxic levels (50-60 &deg;C). Various energy sources are available to heat biological tissues, including radiofrequency (RF) electrical current, microwaves, laser light and ultrasonic waves. Of these, RF and microwave ablation are most commonly used worldwide.
During RF ablation, alternating electrical current (~500 kHz) produces resistive heating around the interstitial electrode. Skin surface electrodes (ground pads) are used to complete the electrical circuit. RF ablation has been in use for nearly 20 years, with good results for local tumor control, extended survival and low complication rates1,2. Recent studies suggest RF ablation may be a first-line treatment option for small hepatocellular carcinoma and renal-cell carcinoma3-5. However, RF heating is hampered by local blood flow and high electrical impedance tissues (eg, lung, bone, desiccated or charred tissue)6,7. Microwaves may alleviate some of these problems by producing faster, volumetric heating8-10. To create larger or conformal ablations, multiple microwave antennas can be used simultaneously while RF electrodes require sequential operation, which limits their efficiency. Early experiences with microwave systems suggest efficacy and safety similar to, or better than RF devices11-13.
Alternatively, cryoablation freezes the target tissues to lethal levels (-20 to -40 &deg;C). Percutaneous cryoablation has been shown to be effective against RCC and many metastatic tumors, particularly colorectal cancer, in the liver14-16. Cryoablation may also be associated with less post-procedure pain and faster recovery for some indications17. Cryoablation is often contraindicated for primary liver cancer due to underlying coagulopathy and associated bleeding risks frequently seen in cirrhotic patients. In addition, sudden release of tumor cellular contents when the frozen tissue thaws can lead to a potentially serious condition known as cryoshock 16.
Thermal tumor ablation can be performed at open surgery, laparoscopy or using a percutaneous approach. When performed percutaneously, the ablation procedure relies on imaging for diagnosis, planning, applicator guidance, treatment monitoring and follow-up. Ultrasound is the most popular modality for guidance and treatment monitoring worldwide, but computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used as well. Contrast-enhanced CT or MRI are typically employed for diagnosis and follow-up imaging.

A thermal tumor ablation procedure is described. The entire procedure is detailed, including pretreatment planning and imaging studies, anesthesia, adjuvant techniques to facilitate a percutaneous approach, imaging guidance of the ablation device to the tumor, thermal treatment, post-treatment care and follow-up.

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

Medicine

Protocol for Long Duration Whole Body Hyperthermia in Mice

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body temperature that is observed during fever. The use of hyperthermia as an adjuvant has emerged as a promising procedure for tumor regression in the field of cancer biology. For this purpose, the most important requirement is to have reliable and uniform heating protocols. We have developed a protocol for hyperthermia (whole body) in mice. In this protocol, animals are exposed to cycles of hyperthermia for 90 min followed by a rest period of 15 min. During this period mice have easy access to food and water. High body temperature spikes in the mice during first few hyperthermia exposure cycles are prevented by immobilizing the animal. Additionally, normal saline is administered in first few cycles to minimize the effects of dehydration. This protocol can simulate fever like conditions in mice up to 12-24 hr. We have used 8-12 weeks old BALB/Cj female mice to demonstrate the protocol.

This paper describes a protocol for whole body hyperthermia in mice that can stimulate fever like conditions up to 12-24 hr.

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body ...

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

Bioengineering

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time imaging and acoustic energy modulation, this modality enables precise temperature control within a defined area. Many thermal applications are being explored with this noninvasive, nonionizing technology, such as hyperthermia generation, to release drugs from thermosensitive liposomal carriers. These drugs can include chemotherapies such as doxorubicin, for which targeted release is desired due to the dose-limiting systemic side effects, namely cardiotoxicity. Doxorubicin is a mainstay for treating a variety of malignant tumors and is commonly used in relapsed or recurrent rhabdomyosarcoma (RMS). RMS is the most common solid soft tissue extracranial tumor in children and young adults. Despite aggressive, multimodal therapy, RMS survival rates have remained the same for the past 30 years. To explore a solution for addressing this unmet need, an experimental protocol was developed to evaluate the release of thermosensitive liposomal doxorubicin (TLD) in an immunocompetent, syngeneic RMS mouse model using MRgHIFU as the source of hyperthermia for drug release.

Presented here is a protocol to use controlled hyperthermia, generated by magnetic resonance-guided high intensity focused ultrasound, to trigger drug release from temperature-sensitive liposomes in a rhabdomyosarcoma mouse model.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time ...

Cancer Research

Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has been challenged. Here, we fabricate iron oxide nanoparticle shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform. Iron oxide nanoparticles serve as both magnetic and photothermal agents. Once intravenously injected, NSMs can be magnetically guided to the tumor site. Ultrasound triggers the release of iron oxide nanoparticles, facilitating the penetration of nanoparticles deep into the tumor due to the cavitation effect of microbubbles. Thereafter, magnetic hyperthermia and photothermal therapy can be performed on the tumor for combinational cancer therapy, a solution for cancer resistance due to the tumor heterogeneity. In this protocol, the synthesis and characterization of NSMs including structural, chemical, magnetic and acoustic properties were performed. In addition, the anti-cancer efficacy by thermal therapy was investigated using in vitro cell cultures. The proposed delivery strategy and combination therapy holds great promise in cancer treatment to improve both delivery and anticancer efficacies.

Presented here is a protocol for the fabrication of iron oxide nanoparticle-shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform for magnetic hyperthermia and photothermal combination cancer therapy.

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has ...

Esophageal Heat Transfer for Patient Temperature Control and Targeted Temperature Management

Controlling patient temperature is important for a wide variety of clinical conditions. Cooling to normal or below normal body temperature is often performed for neuroprotection after ischemic insult (e.g. hemorrhagic stroke, subarachnoid hemorrhage, cardiac arrest, or other hypoxic injury). Cooling from febrile states treats fever and reduces the negative effects of hyperthermia on injured neurons. Patients are warmed in the operating room to prevent inadvertent perioperative hypothermia, which is known to cause increased blood loss, wound infections, and myocardial injury, while also prolonging recovery time. There are many reported approaches for temperature management, including improvised methods that repurpose standard supplies (e.g., ice, chilled saline, fans, blankets) but more sophisticated technologies designed for temperature management are typically more successful in delivering an optimized protocol. Over the last decade, advanced technologies have developed around two heat transfer methods: surface devices (water blankets, forced-air warmers) or intravascular devices (sterile catheters requiring vascular placement). Recently, a novel device became available that is placed in the esophagus, analogous to a standard orogastric tube, that provides efficient heat transfer through the patient&#39;s core. The device connects to existing heat exchange units to allow automatic patient temperature management via a servo mechanism, using patient temperature from standard temperature sensors (rectal, Foley, or other core temperature sensors) as the input variable. This approach eliminates vascular placement complications (deep venous thrombosis, central line associated bloodstream infection), reduces obstruction to patient access, and causes less shivering when compared to surface approaches. Published data have also shown a high degree of accuracy and maintenance of target temperature using the esophageal approach to temperature management. Therefore, the purpose of this method is to provide a low-risk alternative method for controlling patient temperature in critical care settings.

This study presents a novel method to provide efficient patient temperature control for cooling or warming patients. A single use, triple lumen device is placed into the esophagus, analogous to a standard orogastric tube, and connects to existing heat exchange units to perform automatic patient temperature management.

Controlling patient temperature is important for a wide variety of clinical conditions. Cooling to normal or below normal body temperature is often ...

Portable Thermographic Screening for Detection of Acute Wallenberg's Syndrome

Wallenberg&#39;s syndrome (WS) is a type of brainstem infarction. WS patients often show Horner&#39;s syndrome, dissociated sensory disturbance, truncal ataxia, and hoarseness. However, they rarely show tactile sensory disturbance and paralysis of the extremities. Additionally, acute brainstem infarction is often not apparent in magnetic resonance images. These symptomatic and imaging characteristics sometimes lead to misdiagnosis of WS as a non-stroke disease, including auditory vertigo. Although careful neurological examination is necessary to prevent misdiagnosis of WS, this type of examination may be difficult for non-neurologists to whom affected patients initially present. Lateral differences in body surface temperature (BST) constitute a recognized and widespread symptom of WS. We previously reported that most acute WS patients exhibit lateral differences in BST at multiple locations and that these lateral differences in BST could easily be detected by thermographic measurement. Here, we present the method for use of portable thermography to detect acute WS, using a simple, rapid, noninvasive, and cost-effective approach. To assess lateral differences in BST among patients with suspected WS, BST was measured as soon as possible in the examination room or in the patient&#39;s bedroom. Measurements were performed bilaterally at four locations where images could easily be acquired (face, palm of the hand, abdomen, and dorsum of the foot) using a portable thermal camera. When lateral differences in BST are observed macroscopically, especially in multiple locations on the same side, a diagnosis of WS should be suspected. Macroscopic assessment of BST laterality can be made within 2 min of the acquisition of thermographic images. This method may be useful in preventing misdiagnosis of acute WS as a non-stroke disease, especially when such patients initially present to non-neurologists.

Acute Wallenberg&#39;s syndrome can be misdiagnosed as a non-stroke disease, such as auditory vertigo. Thus, careful neurological examination, which is sometimes difficult for non-neurologists, is necessary for precise diagnosis. Here, we present a simple, rapid, noninvasive, and cost-effective method for detection of acute Wallenberg&#39;s syndrome using portable thermography.

Wallenberg&#39;s syndrome (WS) is a type of brainstem infarction. WS patients often show Horner&#39;s syndrome, dissociated sensory disturbance, truncal ...

Neuroscience

Simulating the Influence of a Bipolar Radiofrequency Hyperthermia System on Tumors

A Computational Modeling Approach to Investigate the Influence of Hyperthermia on the Tumor Microenvironment

The biophysical properties of the tumor microenvironment differ substantially from normal tissues. A constellation of features, including decreased vascularity, lack of lymphatic drainage, and elevated interstitial pressure, diminishes the penetration of therapeutics into tumors. Local&#160;hyperthermia within the tumor can alter microenvironmental properties, such as interstitial fluid pressure, potentially leading to improvements in drug penetration. In this context, multi-physics computational models can provide insight into the interplay between the biophysical parameters within the tumor microenvironment and can guide the design and interpretation of experiments that test the bioeffects of local hyperthermia.
This paper describes a step-by-step workflow for a computational model coupling partial differential equations describing electrical current distribution, bioheat transfer, and fluid dynamics. The main objective is to study the effects of hyperthermia delivered by a bipolar radiofrequency device on the interstitial fluid pressure within the tumor.&#160;The system of mathematical expressions linking electrical current distribution, bioheat transfer, and interstitial fluid pressure is presented, emphasizing the changes in the distribution of the interstitial fluid pressure that could be induced by the thermal intervention.

Author Spotlight: Computing the Effects of a Local Radiofrequency Hyperthermia Intervention on Tumor Biomechanics

The article describes a protocol to simulate the transient temperature profiles and the coupled spatiotemporal variation of the interstitial fluid pressure following the heating delivered by a dipolar radiofrequency hyperthermia system. The protocol can be used to assess the response of biophysical parameters characterizing the tumor microenvironment to interventional hyperthermia techniques.

The biophysical properties of the tumor microenvironment differ substantially from normal tissues. A constellation of features, including decreased ...

In Vitro and In Vivo Delivery of Magnetic Nanoparticle Hyperthermia Using a Custom-Built Delivery System

Hyperthermia has long been used in the treatment of cancer. Techniques have varied from the intra-tumoral insertion of hot iron rods, to systemically delivered tumor antibody-targeted magnetic nanoparticles, at temperatures from 39 &#730;C (fever-level) to 1,000 &#730;C (electrocautery) and treatment times from seconds to hours. The temperature-time relationship (thermal dose) dictates the effect with high thermal doses resulting in the tissue ablation and lower thermal doses resulting in sublethal effects such as increased blood flow, accumulation of drugs and immune stimulation. One of the most promising current medical therapies is magnetic nanoparticle hyperthermia&#160; (mNPH). This technique involves activating magnetic nanoparticles, that can be delivered systemically or intratumorally, with a non-invasive, non-toxic alternating magnetic field. The size, construct and association of the magnetic nanoparticles and the frequency and field strength of the magnetic field are major heating determinants. We have developed sophisticated instrumentation and techniques for delivering reproducible magnetic nanoparticle hyperthermia in large and small animal models and cultured cells. This approach, using continuous, real time temperature monitoring in multiple locations, allows for the delivery of well-defined thermal doses to the target tissue (tumor) or cells while limiting non-target tissue heating. Precise control and monitoring of temperature, in multiple sites, and use of the industry standard algorithm (cumulative equivalent minutes at 43 &#730;C /CEM43), allows for an accurate determination and quantification of thermal dose. Our system, which allows for a wide variety of temperatures, thermal doses, and biological effects, was developed through a combination of commercial acquisitions and inhouse engineering and biology developments. This system has been optimized in a manner that allows for the rapid conversion between ex vivo, in vitro, and in vivo techniques. The goal of this protocol is to demonstrate how to design, develop and implement an effective technique and system for delivering reproducible and accurate magnetic nanoparticle therapy (mNP) hyperthermia.

This protocol presents techniques and methodology necessary for the accurate delivery of magnetic nanoparticle hyperthermia using a sophisticated delivery and monitoring system.

Hyperthermia has long been used in the treatment of cancer. Techniques have varied from the intra-tumoral insertion of hot iron rods, to systemically ...

A Standardized Procedure of Dressing Management for Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction with high mortality rates, demanding specialized wound care to address epidermal detachment and bullae formation. This study summarizes a standardized dressing management protocol to enhance the healing process, reduce complications, and improve patient comfort during dressing changes for TEN patients. The protocol emphasizes a systematic approach to patient preparation, environmental control, and the utilization of silver-ion-based dressing materials. Specifically, it integrates gentle cleansing techniques with a warmed povidone-iodine saline solution, precise necrotic tissue removal, and silver sulfadiazine lipid hydrocolloid dressings to maintain an optimal healing environment. The effectiveness of this protocol was further validated through a retrospective analysis, which showed a significant reduction in the onset of re-epithelization, wound healing time, and hospital stays, resulting in diminished pain during dressing changes. Furthermore, this protocol also provides tailored strategies for dressing changes in sensitive areas, ensuring comprehensive care. The standardized protocol streamlines the dressing process and contributes to more efficient allocation of healthcare resources, establishing a robust foundation for TEN treatment that can be adopted in clinical practice and inform future research.

This is a standardized dressing protocol for patients with toxic epidermal necrolysis. This robust protocol utilizes silver ion dressings designed to accelerate healing and alleviate pain, minimizing hospital stays.

Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction with high mortality rates, demanding specialized wound care to address ...