Local Hyperthermia for Warts Treatment

Podsumowanie

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.

Streszczenie

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.

Wprowadzenie

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 outcomes^8,9. 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.

Protokół

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

1. 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.
   1. 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.
2. 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.

2. Target skin lesion selection

1. For an individual skin lesion, adjust the angle and elevation as needed and apply targeted treatment directly to the lesion (Figure 1).
2. 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.
3. 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.
4. 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.

3. Hyperthermia treatment

1. 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's operating screen. The machine allows for the treatment of one patient at a time, and the following are the specific steps for operation.
2. Access the registration form: Navigate to the registration module within the machine's interface. Enter the patient'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.
3. 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.
4. 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 °C on Level 1 and increasing to 46 °C on Level 9 (Figure 2A).
5. Mode selection: Choose the appropriate treatment mode from the options provided by the machine based on the patient'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'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.
   1. Mode one: This mode increments the temperature by 1 °C every 3 min, with each pulse lasting for 10 s.
   2. Mode two: This is similar to mode one, but each pulse lasts for 20 s, providing a longer exposure to the increased temperature.
   3. Mode three: This mode accelerates the temperature rise to 2 °C per pulse, with each pulse sustained for 20 s, maintaining a consistent 3 min interval between pulses.
   4. To initiate the treatment, configure the device settings to Mode two at Level 5 (which corresponds to a temperature of 43 °C). This configuration has been established^12,13 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's tolerance playing a crucial role in its determination.
6. 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.
7. Assist the patient in positioning properly. Guide the patient to a comfortable and stable position that allows for effective treatment without discomfort.
8. 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.
9. Fine-tune the mechanical arm using the cross switch. Maintain a standard distance of 5 cm between the device head and the lesion.
   1. 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.
10. Initiate the irradiation process. Once the mechanical arm is correctly positioned, click the Start button to begin the treatment session.
11. Treatment monitoring: During treatment, assess the patient'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'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.
    1. 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.
    2. 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.
12. Treatment termination: The remaining time will be continuously displayed during the treatment process. Upon reaching the set duration, the device'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.

4. Treatment plan

1. The specific therapeutic protocol is illustrated in Figure 3. Typically, the initial treatment period lasts for 15 ± 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 ± 3 days.
2. 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.
3. 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.
4. Following an initial period of 2-3 min to assess the patient's tolerance, adjust the treatment intensity in accordance with the observed response.

5. Precautions

1. In cases where the patient exhibits hypersensitivity to the initial short-term exposure, immediately reduce the treatment intensity to minimize the risk of blistering.
2. Keep each treatment session at 30 min, ensuring consistent perpendicular irradiation directed at the target lesion throughout the entire duration.
3. To ensure the induction of an immune response, predicate the choice of modality and intensity on the patient perceiving a mild pricking sensation.
4. If a blister does form, manage it appropriately and resume treatment once the blisters have fully resolved.
5. The application of hyperthermia is contraindicated for skin areas with open wounds.
6. 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.
7. Ensure the selection of warts for hyperthermia treatment targets areas that are relatively flat and facilitate perpendicular irradiation.

Wyniki

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 articles^13,14,15. They found that hyperthermia was also associated with reduced pain during treatment h...

Dyskusje

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...

Materiały

Name	Company	Catalog Number	Comments
YY-WRY-V02 infrared specific wave photothermal therapeutic instrument	Liaoning Yanyang Medical Equipment Co., Ltd	No. ZL200720185403.3, China Medical University, China)