*4.11.1 Carbon dioxide (CO2) laser*

The CO2 laser was the initial laser modality used to treat warts and has been used since 1980s [39–41]. The CO2 laser emits infrared light of wavelength 10,600 nm. It is absorbed by tissue water and results nonselective thermal tissue destruction. The CO2 laser treats warts via two mechanisms. A focused CO2 laser beam used as a scalpel to excise the wart down to the subcutaneous tissue, followed by the base of the wart, which is vaporised by a defocused beam until a clean surgical field is obtained [42–45]. Cohort studies report that simple and recalcitrant common, palmar, plantar, periungual and subungual warts have been successfully treated with CO2 laser, with response rates ranging from 50 to 100% [40, 43, 46–53]. Usually, excision by focused mode followed by vaporisation and haemostasis with defocused mode is the common practice. Deeper warts need more passes. Using two to four passes per wart is adequate [46–49]. CO2 laser treatment may be used for recalcitrant warts but also as a first-line of therapy for warts—mainly in the sole, hands and other parts also [46]. Single verruca lesions usually result better (66.7%) than multiple verruca (62.5%) [46]. It can be used for first-line therapy for periungual and subungual warts. It has been seen that patients with subungual and periungual warts, who have failed previous conventional therapy, respond less than in patients when CO2 laser therapy was given as first line (47.9% compared to 80.0%) [47]. Subungual warts respond better than periungual warts [47]. Usually one or two sessions are adequate [48]. Patients with one session heal earlier than patients with more than one session [48]. Adverse effects include permanent nail matrix damage and scarring, and nail changes such as distal onycholysis and thickening may occur [47, 48, 51]. CO2 laser may also be used as excision tool, with a remission rate of 95.5%, but requires specialised unit [49]. Scarring is a possibility [49]. 'En bloc' excision of wart is very much effective [100%] in paediatric age group also with no recurrence, and usually single session is adequate [50]. Many treatment modalities are not feasible in immunosuppressive patients. CO2 laser can be a safe and comparably effective modality of treatment, even in one intervention [51]. Complete excision of the lesional skin with a portion of deeper tissue and 1-mm non-lesional margin leads to the complete clearance of HPV DNA, which leads to very lower recurrence, though chance of scar formation is there. Dressing with artificial dermis leads to less scar formation [52]. Application of Imiquad after CO2 laser in recalcitrant wart reduces or stops recurrences [53]. Vapour produced by CO2 laser with any power density and fluence contains intact papillomavirus DNA. This infected vapour may cause pulmonary infection [54]. Plume produced from laser procedure collected and used as inoculum may produce identical lesions [55]. So, safety precautions during laser surgery may be strictly maintained [55]. It is important to wear surgical masks as it is capable of removing all laser- or electrocoagulation-derived viruses [56], even gas scavenging system to be in use [57]. But a study among CO2 laser surgeons in all the members of American Society of Laser Medicine shows that the plume does not possess enough infectious material to produce significantly more amount of warts in laser surgeons in comparison to population-based common subjects [58]. But, sitewise, CO2 laser surgeons have a greater risk of acquiring nasopharyngeal lesions, especially when they treat genital warts with HPV types 6 and 11 [58]. Scar formation is a known side effect of CO2 lasers, and there are more chances of hypertrophic scar formation if the patient is on cyclosporine for other reasons [59]. In superpulsed CO2 LASERs, the high irradiances and brief duration make possible very precise removal of target lesion volumes and controlled excision. Here, thermal damage is very less leading to less inflammation and less scarring [60].

## *4.11.2 Erbium:yttrium/aluminium/garnet (Er:YAG) laser*

Non-ablative lasers are largely replacing ablative CO2 lasers as side effects are less, both for patients and clinicians [61]. Er:YAG laser emits 2940 nm wavelength. It is absorbed 12–18 times more efficiently by water containing superficial cutaneous tissue than CO2 laser. At 250 microsecond pulse duration and 5 J/cm2 fluence short pulse, Er:YAG laser ablates 5–20 micrometre of tissue per laser pass, and minimal residual thermal damage that results faster tissue re-epithelialization and less side effects. The disadvantage is intraoperative bleeding [62]. Its mechanism of action in treating warts is through direct ablation of the lesion in the epidermis, layer by layer until normal tissue is visualised. This laser type also has bactericidal effects [61]. Er:YAG laser was tried in all types of common warts—periungual, subungual and plantar warts; complete clearance rate was 68% for plantar warts, 78% for periungual warts and 76% for subungual warts. In patients with extensive involvement, more than one session were needed. Relapse was only in plantar wart patients (17.8%) [62]. Chance of scarring is less in Er:YAG laser [62, 63]. For hard-totreat palmoplantar warts, a combination of ablative Er:YAG laser and topical 0.5% podophyllotoxin solution yields higher success with complete clearance of 88.6% without any pigmentary changes, wound infection and scarring. Relapse rate is also less [64]. Er:YAG laser procedure can be done without anaesthesia or with topical cream anaesthesia as there is minimal pain, except only in large, very thick plaque in the plantar or palm. The plume contains no viral DNA [65]. Side effects are less with Er:YAG laser, no hyper- or hypopigmentation and no post-operative infection. Healing is very fast, within 7–10 days. Redness persists up to 3 months [66]. In a study of 69 patients with difficult-to-treat warts (periungual or plantar), 72.5% of patients with wart observed complete response (CR) irrespective of the duration of infection with HPV or the age of the patients. Plantar warts were more resistant (13.5% non-responders) than periungual warts (5.9% non-responders), and larger mosaic plantar warts were less sensitive than single warts; 24.0% of patients showed relapse [67]. Wound healing may be assisted/accelerated with LED phototherapy (633 nm). Immediately after Er:YAG ablation, with precise removal of wart tissue, a red LED therapy system is applied (633 nm, 20 min, 96 J/cm2 ) to the wound and surrounding area, LED system with same parameters were repeated on the second, sixth and tenth post-operative day. On the sixth post-operative day, the wound has shrunk noticeably and is filled with healthy, granulation tissue, and on day 15, the wound healed completely with minimal scarring; recurrence rate was also less (<6%) [68].

### *4.11.3 Neodymium:YAG (Nd:YAG) laser*

Principal emission of Nd:YAG is at 1064 nm, in the infrared range [Nd:YAG produces heat]. Heat therapy depends on the principle that diseased tissue which is being treated is more sensitive to the effects of the elevated temperature than normal tissue and this is less able to recover after heat exposure [69]. Side effects such as coagulation, blister or crusts are less after hyperthermia. Response is excellent (77%), though in 23% of the method failed, and there is no recurrence in 9 months follow-up. Nd:YAG can be used in all types and site warts including periungual, hand and plantar warts [70]. HPV DNA becomes completely absent in hyperthermia-treated wart lesions, in comparison to cryotherapy where 96% wart lesions are positive for HPV DNA by in situ hybridization [71]. The light of the solid state Nd:YAG laser can easily be guided by fibres to tissue and perform good coagulation and homeostatic function, in laryngeal, as well as genital, easily and more precisely. Its continuous suction endures a minimal load of potential infectious laser plume [72]. For therapeutic treatment, Nd:YAG laser can be utilised

**39**

*4.11.4 Pulsed dye laser*

*Human Papillomavirus Infection: Management and Treatment*

for genital tract lesion and cervical conization for early neoplasms like dysplasia, carcinoma in situ and microinvasive carcinoma [73, 74]; these are caused by HPV infections. Invasive lasers like CO2 are normally considerably more painful and require longer recovery time, and also side effects like scarring are high. A long pulsed Nd:YAG laser emits 1064 nm wavelength light, in infrared spectrum, in longer wavelength with lower haemoglobin, and melanin absorption coefficients allows deeper delivery of higher energy in hyperkeratotic and thicker epidermis that are assisted with warts [75]. Several studies have evaluated the use of the Nd:YAG laser in the treatment of simple and recalcitrant common, palmoplantar, periungual and subungual warts, with efficacies ranging from 46 to 100% [61, 76–78]. Laser protocol varied among different studies: spot size between 3 and 7 mm, pulse

between 1 and 8, treatment interval from 2 weeks to 12 months and mean number of treatments between 1.49 and 4.65. In a study of Han et al. [76], 348 patients of all types of simple and recalcitrant common, palmoplantar and periungual warts are treated with Nd:YAG laser (spot size, 5 mm; pulse duration, 20 ms; 200 J/cm<sup>2</sup>

no cooling; 1–2 pulses). After a mean of 1.49 treatments, wart clearance rate was 96% though there were differences in clearance rates after initial treatment depending on location (72.6% for common warts vs. 44.1% for palmoplantar warts) [76]. For determination of effectiveness and safety of a novel 100 microsecond pulsed 1064 nm Nd:YAG laser in treatment of Verruca vulgaris, low energy (200 mjouls) Nd:YAG, in monthly intervals for 3 months was given to 25 patients with lesion on hands-nineteen patients had complete clearance; with minimal discomfort [61]. At least partial response (50% reduction) in verruca size was noticed in all lesions [61]. Aggressive treatment of hand warts may cause tissue damage. To avoid the tissue damage, a novel modification was tried [77]. Fifty one recalcitrant verrucas were treated with ND:YAG laser; all warts were administered in at least three pulses. The circle of pulses given in that way that the three circles overlapped each other only on the site of verruca- so that highest level of energy reached only to the wart. The adjacent tissue can avoid unintended tissue damage [77]. All lesions subsided, 88.35% lesions in one laser session, remaining patients were required two laser sessions- those lesions were periungual and palmar. There was no recurrence in 12 months follow-up, no major side effects, no nail dystrophy or severe post-treatment

scarring. Hyperpigmentation was present in 5.48% patients [77].

Among non-ablative modalities, pulsed dye laser (PDL) can be used for a selective, non-bloody destruction of extragenital and genital warts [79]. It emits a wavelength of 585, which is absorbed by haemoglobin and oxyhaemoglobin [79, 80]. Mechanism of action is unclear, but may be a result of intense heating of dermal vessels that leads to damage of viral DNA-containing keratinocytes. The theory is based on the presence of dilated and congested vessels at the base of most verruca and the mechanism of selective photothermolysis that results in the targetting of haemoglobin by the PDL [80]. The heat and immunological process and the removal of the blood supply to the wart may be the reason for the effectiveness of PDL in verruca therapy, but it is not above controversy [81]. This selective damage to blood vessels, sparing unnecessary damage to healthy adjacent cellular structure, avoids the scarring [82]. The local dermal vascular destruction of the warts stimulates cell-mediated immune response that is important for eradication of viral warts [83]. So, PDL for wart therapy, even in facial wart, is attractive [84] for its efficient and cosmetic resolution [84, 85]. The PDL is usually painless or minimally painful like snapped by a rubber band [86], though some patients complain of severe

, cooling methods, number of pulses

;

*DOI: http://dx.doi.org/10.5772/intechopen.92397*

duration of 1–20 ms, fluence of 100–200 J/cm2

### *Human Papillomavirus Infection: Management and Treatment DOI: http://dx.doi.org/10.5772/intechopen.92397*

for genital tract lesion and cervical conization for early neoplasms like dysplasia, carcinoma in situ and microinvasive carcinoma [73, 74]; these are caused by HPV infections. Invasive lasers like CO2 are normally considerably more painful and require longer recovery time, and also side effects like scarring are high. A long pulsed Nd:YAG laser emits 1064 nm wavelength light, in infrared spectrum, in longer wavelength with lower haemoglobin, and melanin absorption coefficients allows deeper delivery of higher energy in hyperkeratotic and thicker epidermis that are assisted with warts [75]. Several studies have evaluated the use of the Nd:YAG laser in the treatment of simple and recalcitrant common, palmoplantar, periungual and subungual warts, with efficacies ranging from 46 to 100% [61, 76–78]. Laser protocol varied among different studies: spot size between 3 and 7 mm, pulse duration of 1–20 ms, fluence of 100–200 J/cm2 , cooling methods, number of pulses between 1 and 8, treatment interval from 2 weeks to 12 months and mean number of treatments between 1.49 and 4.65. In a study of Han et al. [76], 348 patients of all types of simple and recalcitrant common, palmoplantar and periungual warts are treated with Nd:YAG laser (spot size, 5 mm; pulse duration, 20 ms; 200 J/cm<sup>2</sup> ; no cooling; 1–2 pulses). After a mean of 1.49 treatments, wart clearance rate was 96% though there were differences in clearance rates after initial treatment depending on location (72.6% for common warts vs. 44.1% for palmoplantar warts) [76]. For determination of effectiveness and safety of a novel 100 microsecond pulsed 1064 nm Nd:YAG laser in treatment of Verruca vulgaris, low energy (200 mjouls) Nd:YAG, in monthly intervals for 3 months was given to 25 patients with lesion on hands-nineteen patients had complete clearance; with minimal discomfort [61]. At least partial response (50% reduction) in verruca size was noticed in all lesions [61]. Aggressive treatment of hand warts may cause tissue damage. To avoid the tissue damage, a novel modification was tried [77]. Fifty one recalcitrant verrucas were treated with ND:YAG laser; all warts were administered in at least three pulses. The circle of pulses given in that way that the three circles overlapped each other only on the site of verruca- so that highest level of energy reached only to the wart. The adjacent tissue can avoid unintended tissue damage [77]. All lesions subsided, 88.35% lesions in one laser session, remaining patients were required two laser sessions- those lesions were periungual and palmar. There was no recurrence in 12 months follow-up, no major side effects, no nail dystrophy or severe post-treatment scarring. Hyperpigmentation was present in 5.48% patients [77].

### *4.11.4 Pulsed dye laser*

Among non-ablative modalities, pulsed dye laser (PDL) can be used for a selective, non-bloody destruction of extragenital and genital warts [79]. It emits a wavelength of 585, which is absorbed by haemoglobin and oxyhaemoglobin [79, 80]. Mechanism of action is unclear, but may be a result of intense heating of dermal vessels that leads to damage of viral DNA-containing keratinocytes. The theory is based on the presence of dilated and congested vessels at the base of most verruca and the mechanism of selective photothermolysis that results in the targetting of haemoglobin by the PDL [80]. The heat and immunological process and the removal of the blood supply to the wart may be the reason for the effectiveness of PDL in verruca therapy, but it is not above controversy [81]. This selective damage to blood vessels, sparing unnecessary damage to healthy adjacent cellular structure, avoids the scarring [82]. The local dermal vascular destruction of the warts stimulates cell-mediated immune response that is important for eradication of viral warts [83]. So, PDL for wart therapy, even in facial wart, is attractive [84] for its efficient and cosmetic resolution [84, 85]. The PDL is usually painless or minimally painful like snapped by a rubber band [86], though some patients complain of severe

intraoperative pain [87, 88], so local anaesthesia may be required. Purpura may develop due to sudden burst of wart vasculature—that develops within minutes in the treated areas—which takes 10–14 days to subside spontaneously [88]. Even perianal warts in child patients are also treatable with PDL without any complications and with 100% clearance [89]. Verruca plana lesions on face in Asian (type IV-V skin) clear completely with PDL without producing significant pigmentary and textural complications [90]. Safety is one of the major advantages of this technique [91]. But the absence of any proven superiority over the standard treatments in terms of efficacy, coupled with high costs, means that PDL should only be used as second-line therapy in patients with cosmetic needs [91].

Laser protocols are different in all studies, and variation of results may be for that reason. Different protocols include spot size of 5–10 mm, fluence of 5 j/m2 –15 j/m2 , pulse duration of 38 ns–1.5 ms, consecutive 2–3 pulses with overlap of 1–2 mm, 1–12 sessions, interval of 2–4 weeks and cooling methods [90–98]. In immunocompetent children, the overall response rate is 75%, and the remaining 25% had partial clearance, with an average number of treatment for complete clearance to be 3.1—face and perineum are areas most likely to be cleared in one treatment (50 and 20%, respectively) [99, 100]. It is also a more effective therapy especially against those that have not been eradicated by other treatments [101]. Though less, adverse effects are also not very much uncommon, about 8.2% of patients had adverse effects like wound formation (3.8%), residual scarring (2.9%), infection (1.0%) and collapse (0.5%); 63% of patients had excessive pain [97]. But opinion about pain and patient compliance are different in other study [102]. Here only 6.34% of patients classified the method as too painful and withdrew after the first one or two treatments They have concluded that FPDL is safe and effective for the removal or reduction of verrucae vulgares, and requires less patient compliance compared with other treatment options. PDL followed by intralesional Bleomycin gives very good result with complete clearance, even in immunosuppressive patients, though the overall treatment session was high (1.8 vs. 3) [98], but should be aware of common side effects seen such as painful haemorrhagic blistering and superficial ulceration [103].

### *4.11.5 Potassium titanyl phosphate (KTP) laser*

The KTP laser has been utilised in the treatment of recalcitrant cutaneous warts, and when treated to complete clearance, no recurrence occurred [104].
