The Laryngoscope Lippincott Williams & Wilkins, Inc., Philadelphia © 1999 The American Laryngological, Rhinological and Otological Society, Inc.

Laser Management of Oral Leukoplakias: A Follow-up Study of 70 Patients

Michael L. Schoelch, DMD; Nahid Sekandari, DDS; Joseph A. Regezi, DDS, MS; Sol Silverman, Jr., MA, DDS

Objectives/Hypothesis: To assess the efficacy of laser therapy for the management of premalignant oral lesions. Study Design: The study group consisted of seventy consecutive laser-treated patients with oral leukoplakia. The microscopic diagnosis included idiopathic focal keratosis, dysplasias of all grades, and verrucous hyperplasia (proliferative verrucous leukoplakia). Thirty-nine patients had some degree of microscopic dysplasia and six demonstrated high­risk proliferative verrucous leukoplakia. The clinical appearances of the lesions were white (homogeneous leukoplakia) in 48, red and white (erythroleukopla­kia) in 8, and verrucous in 14. There were 38 men and 32 women in this group. The average age was 63 years (range, 31-90 y). Methods: Lasers employed were the C02 and Nd:YAG lasers, and standard laser safety protocols were used. Results: There was no postoper­ative infection, hemorrhage, or paresthesia. Two pa­tients developed pyogenic granulomas in their surgi­cal sites. Fifty-five of 70 patients were followed for more than 6 months; follow-up averaged 32 months (range 6-178 mo). Twenty-nine patients had complete control of their lesions; 19 patients had small recur­rences removed with subsequent laser surgeries, leading to control; 2 patients had complete recurrenc­es; and 5 patients developed squamous cell carcinoma at the lesion site. Verrucous lesions had an especially high rate of recurrence (83%), with 9 of 12 ultimately controlled with subsequent surgeries. Conclusions: Laser surgery of oral leukoplakia is an effective tool in a complete management strategy that includes careful clinical follow-up, patient education to elimi­nate risk factors and report suspicious lesions, and biopsy of suspicious lesions when appropriate. How­ever, recurrence and progression to cancer remain a risk. Key Words: oral cancer, laser, C02 , Nd:YAG, leukoplakia.

Laryngoscope, 109:949-953, 1999

From the University of California, Department of Stomatology, School of Dentistry, San Francisco, California.

Editor's Note: This Manuscript was accepted for publication Febru­ary 1, 1999.

Send Reprint Requests to Michael L. Schoelch, DMD, 11331 Lake­shore Drive, Pleasant Prairie, WI 53158, U.S.A. E-mail: msonnet@ acronet.net

Laryngoscope 1 09: June 1999

INTRODUCTION Oral idiopathic leukoplakia is well established as

being at risk of transforming to carcinoma.1- 3 Other re­lated oral lesions, erythroleukoplakia (red and white le­sion) and proliferative verrucous leukoplakia (exophytic and expanding lesion), carry an even greater risk for ma­lignant transformation.1- 6 Therefore, proper diagnosis and effective removal might aid in the prevention of some oral cancers. Since its introduction in the early 1970s in endoscopic surgery of the larynx,7 the C02 laser has be­come useful in a variety of soft tissue surgical procedures, including the excision of malignant and leukoplakic le­sions of the oral cavity.8 - 13 The Nd:YAG laser has also been applied with success to the treatment of other oral mucosal lesions.14.15 In a previous study the safety and efficacy of the C02 and Nd:YAG lasers were demonstrated in a variety of oral mucosal pathologies.16 Laser surgery is associated with little morbidity, low intraoperative and postoperative complication rates, and disease control com­parable to or better than conventional methods of man­agement. The purpose of this current study was to further evaluate the use and outcome oflaser energy as a surgical modality in the management of oral premalignant lesions.

MATERIALS AND METHODS The study group comprised 70 patients treated in a

university-based outpatient oral medicine clinic. Inclusion crite­ria were the following: 1) Clinical presentation of idiopathic le­sions with white (homogeneous leukoplakia), red and white (erythroleukoplakia), or proliferative verrucous leukoplakia; 2) a biopsy prior to laser removal; and 3) no prior history of oral carcinoma. Microscopic degrees of dysplasia were calibrated on the basis of the World Health Organization guidelines.17 Prior to both biopsy and laser removal, vital staining with 1% aqueous toluidine blue and decolorization with 1% acetic acid were used to aid in biopsy sampling and detection of surgical margins.1s All surgeries were performed under local anesthesia on an outpatient basis by trained laser dentists following the educational stan­dards established by the Curriculum Guidelines and Standards for Dental Laser Education. 19

Surgical intent was to remove the lesions with margins of clinically healthy-appearing mucosa. Two laser emission wave­lengths were utilized: 10,600 nm (C02) and 1,064 nm (Nd:YAG). The C02 laser device utilized was an articulated arm-delivered surgical C02 laser equipped with an intra-oral handpiece (Xanar,

Schoelch et al. : Laser Management of Oral Leukoplakias

949

Coherent Medical Group, Palo Alto, CA), a power range of 1 to 20 W, continuous wave, and a beam diameter 0.8 to 1.5 mm. Two pulsed fiber-optic-delivered Nd:YAG lasers were utilized: 1) the dLase 300 (manufactured for American Dental Laser of Troy, MI by Sunrise Technologies, Inc., Fremont, CA), with a power range of 0.3 to 3 W and a repetition rate of 10 to 30 Hz, and 2) the Sunlase Master (Sunrise Technologies), with a power range of0.3 to 10 W and a repetition rate of 10 to 100 Hz.

The C02 laser was used for more extensive lesions owing to its larger spot size and continuous mode. The Nd:YAG laser was used in lesions adjacent to hard tissue, owing to its smaller spot size and fiberoptic contact delivery, which offer more precise control of laser energy adjacent to noninvolved tooth structures. The C02 laser was used in a noncontact mode with a range of power from 3 to 10 W. The Nd:YAG was used in both a contact mode (for excision) and a noncontact mode (for coagulation), with a range of 2 to 8 W at 20 to 50 Hz. Laser power settings were selected by the dentist operator according to the extent of the lesion and the treatment objective (coagulation, excision, or vaporization).

The excision sites were left to granulate and undergo heal­ing by secondary intention. Large(> 2 em) lesions were treated in planned serial visits to reduce postsurgical dysfunction and pain. For each surgical procedure, the clinical extent of the lesion treated was documented by either photograph and/or drawings in the patient record. Clinical examination and postoperative pho­tography were utilized to monitor changes during the follow-up period. Appropriate postoperative instructions, including use of analgesics, management of postoperative complications such as edema and hemorrhage, oral hygiene, and diet were provided to each patient. In selected cases of medically compromised patients or treatment of extensive lesions, postoperative antibiotics were prescribed. Nonnarcotic or narcotic analgesics were prescribed as needed for postoperative pain. Patients were followed at 1 week after surgery, and at monthly intervals thereafter. At all times during treatment and follow-up, patients were instructed to re­port any change in signs and symptoms, and if necessary, addi­tional follow-up examinations were scheduled.

RESULTS Some lesions involved multiple sites; the locations

were as follows: tongue, 39; gingiva, 13; buccal mucosa, 10; floor of mouth, 10; lower lip, 8; palate, 3; lower labial mucosa, 1. The clinical and microscopic findings for the 70 patients at the time of initial presentation for laser man­agement showed that 39 had some degree of microscopic dysplasia, and 6 had proliferative verrucous leukoplakia

(Table 1). Lesions with a red component showed dysplasia more frequently than leukoplakias (88% vs. 60%, respec­tively). Twenty-eight patients complained of pretreatment pain described most often as soreness or burning. In some cases, the differential diagnosis included vesiculoerosive inflammatory disease and/or candidiasis, and empiric therapy with topical steroids and/or antifungals failed to resolve the lesion. Forty-five of 70 patients had a histo­logic diagnosis of dysplasia (mild, moderate), severe (car­cinoma in situ), or atypical verrucous proliferation.

Table II outlines the treatment parameters for all three types of lesions. In several cases, the C02 laser was utilized after the Nd:YAG failed to control a proliferative verrucous leukoplakia, since more laser energy was re­quired to control the spread of the lesion. As expected, proliferative verrucous leukoplakias required the largest number of treatments to effectively control the lesion, owing to this lesion's tendency to spread as well as recur at a rapid rate. Although 15 patients complained of pain of longer than 1 week in duration, in no case was pain of more than a moderate level at 2 weeks after surgery, and no patient required analgesics of any kind after 2 weeks. Eleven of 15 patients complained of moderate pain involv­ing lesions on the lateral tongue. No cases of postoperative infection or paresthesias were reported, and no cases of severe hemorrhage intraoperatively. Two pyogenic gran­ulomas developed after surgery in two patients, and both healed uneventfully.

Fifty-five patients were available for follow-up anal­ysis (Table III). Follow-up was limited in 15 patients be­cause of the following: 7 could not be located; 6 were contacted but unable to return, although they reported no recurrent disease; and 2 required additional treatment. Disease was controlled in 29 (53%) with one to five planned surgeries, with no recurrence, and showed some clinical control in 19 (35%), with small areas of recurrence (usually less than 5 mm in diameter) that were controlled with subsequent surgery, or clinically monitored with no progression of disease. Complete recurrence was seen in 2 of 55 patients (4%), and no further laser surgery was attempted.

In examining the patients with recurrences after la­ser excision, no associations could be found with either the

TABLE I. Clinical Characteristics of 70 Patients at Time of Presentation for Laser Management of Premalignant Oral Epithelial Lesions.

Age (y) Sex Duration of Lesion (mo) Tobacco

Clinical Appearance No. Range Mean M F Uset Range Mean

Leukoplakia 48 31-90 63 27 21 26 1-252 51

Erythroleukoplakia 8 43-85 69 5 3 4 1-72 31

Proliferative verrucous leukoplakia 14 35-81 60 6 8 6 2-180 63

70 31-90 63 38 32 36 1-252 51

Characteristics tabulated according to clinical appearance. tTobacco use: history of the equivalent of > 1 pack of cigarettes per day for a minimum of 1 year. :j:Patient complained of painful symptoms associated with the lesion at the time of initial presentation.

Pain:j:

18

3

7

28

Lesion Size (em) Histopathology

1-2 > 2 FK MD CIS

19 29 19 24 5

4 4 2 5

3 11 5 2 1

26 44 25 28 11

FK = focal keratosis; MD = mild to moderate dysplasia; CIS - severe dysplasia to carcinoma in situ; AVP = atypical verrucous proliferation.

AVP

6

6

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Schoelch et al.: Laser Management of Oral Leukoplakias

TABLE II. Treatment Parameters of 70 Patients With Premalignant Oral Epithelial Lesions.

Postoperative Laser Therapy Treatments (n) Post-Laser Medications• Paint

Clinical Appearance No. ND:YAG co, Both:j: Serial§ Range Mean Antibiotic Analgesic 0 2

Leukoplakia 48 12 28 8 14 H7 2.3 39 35 20 18 10 Erythroleukoplakia 8 7 0 1-2 1.5 7 7 4 3 Proliferative verrucous leukoplakia 14 7 7 7 HO 4.7 14 13 4 6 4

70 12 42 16 21 1-17 2.7 60 55 28 27 15

·Antibiotic was used prophylactically; analgesic varied from nonsteroidal to acetaminophen-codeine; some patients used analgesics prophylactically. tPain: 0 - minimal or no pain during first postoperative week; 1 = minimal to moderate pain of less than 1 week's duration; 2 ~ moderate to severe pain

of greater than 1 week's duration. :j:Based on availability of unit or Nd:YAG failure to control lesion. §Planned serial laser surgeries.

location of the lesion or type oflaser utilized. Recurrences typically occurred adjacent to the surgical site, and ap­peared to develop from clinically normal-appearing mu­cosa in a range of 1 to more than 12 months after surgery. As might be expected, lesions with a histologic diagnosis of some degree of dysplasia had a greater risk for recurrence than those with no dysplasia; but the proliferative verru­cous leukoplakias had the highest frequency of recurrence (Table Ill). Although initial treatment success was poorest

in patients with proliferative verrucous leukoplakia, even­tually control of disease progression was obtained in 9 of 12 patients, following periodic subsequent minor laser surgeries to eradicate small recurrences, typically adja­cent to the previous surgical site.

There was progression to squamous cell carcinoma in 5 cases (9%) at the lesion site (Table III). In the prolifer­ative verrucous leukoplakia group, 2 of 12 patients (17%) developed a carcinoma, and in the combined leukoplakias

TABLE Ill. Clinical Outcome Results for 55 Patients Followed for More Than 6 Months After

Laser Management of Oral Premalignant Epithelial Lesions.*

Clinical Appearance/Histology

Length of Postoperative Follow-up (mo)

One No. Range Mean Surgery

Clinical Outcome

Lesion Control With

Planned Serial Surgeries

Small Recurrences Removed With Subsequent Surgeries

Failure Due to

Complete Disease Progression Recurrence (Malignant Conversion)

--------------------------------------------------------------Leukoplakia

FK

MD

CIS

Erythroleukoplakia

FK

MD

CIS

16 6-68 16 6-83 5 6-49

37 6-83

0 2 10-11 4 9-12

6 6-13 Proliferative verrucous leukoplakia

FK 4 13-70 MD

CIS AVP

Total

2 48-81 1 11 5 6-178

12 6-178

55 6-178

28 32 28

30

11 12

12

37 65 11 60

49

32

9

2

0

11

0

2

2

0

0

0

0

13

4

6

2

12

2

0

0

0

2

2

16

•Results tabulated according to clinical appearance and histologic diagnosis.

3

5

2

10

2

4

0

2

7

19

0

0

0

0

0

0

0

0

2

0

2

3

0

0

0

0

0

1

2

5

FK - focal keratosis; MD = mild to moderate dysplasia; CIS = severe dysplasia to carcinoma in situ; AVP = atypical verrucous proliferation.

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TABLE IV. Clinical Features of Five Patients With Malignant Transformation to Squamous Cell Carcinoma.

Patient No. Age (y) Sex Smoker Clinical Appearance

71 F N Verrucous leukoplakia

2 75 F y Erythroleukoplakia

3 76 M y Leukoplakia

4 52 M y Leukoplakia

5 51 M y Leukoplakia

*Site of premalignant lesion and carcinoma the same. tCarcinomas controlled with surgery and/or radiation.

and erythroleukoplakias group, 3 of 43 (7%) transformed into carcinoma (Table IV). In all five patients carcinoma developed in the site of previous laser surgery in an aver­age of 26 months (range, 4 - 78 mo) after the time of sur­gery.

DISCUSSION Laser excision of precancerous oral epithelial lesions

offers comparative advantages over traditional scalpel ex­cision. These advantages include rapid removal of dis­eased tissue, control of bleeding, precise removal of le­sional tissue, good patient acceptance, low morbidity and complications, and favorable healing. Because of the low morbidity and reasonably effective control, laser removal by vaporization or excision appears useful in oral cancer control. This potential approach to prevention is impor­tant, because the mortality from oral cancer is high: about half of those affected with oral cancer will die of their disease.

The key element in the success of laser management is its precise ability to remove mutagenic clones from the oral mucosa as they develop. Although it remains unre­solved whether control ofleukoplakia by surgical removal prevents the development of cancer in that site, this hy­pothesis certainly appears logical. Once epithelial cells have shown mutations in tumor suppressor genes or proto-oncogenes, they have an established risk of malig­nant progression over time. In relatively short-term follow-up, our findings so far indicate a possibility of pre­vention. Until effective therapies are developed that can either 1) prevent these mutations, 2) reverse these muta­tions or 3) arrest further malignant progression, the most definitive method of prevention is the recognition and excision of these mutagenic clones as they are detected.

Certainly, attempts at removing dysplastic leukopla­kias are important, because the risk for malignant trans­formation is relatively high. However, even leukoplakias that histologically show microscopic hyperkeratosis are at risk for malignant transformation. But the highest risk appears to be with proliferative verrucous leukoplakia, and these lesions should be removed surgically. In exten­sive or multifocal lesions, serial removal is reasonable, acceptable, and effective. It should be emphasized, how­ever, as with any destructive modality done without

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lime After Laser Location• Histology Surgery (mo)t

Gingiva, mandibular Severe dysplasia 13

Up, lower Aty~ical verrucous 78 pro iteration

Tongue, lateral Severe dysplasia 4 Lip, lower Moderate 19

dysplasia

Tongue, ventral Moderate 17 dysplasia

pathologic examination of margins, that there is always the possibility of incomplete removal. Close clinical follow-up is necessary to detect early recurrence.

Early detection of premalignant oral lesions is aided by careful clinical examination and thorough follow-up of high-risk patients. This process includes follow-up biopsy when changes in signs or symptoms occur. Exfoliative cytology and vital staining with toluidine blue are useful clinical adjuncts to supplement clinical judgment. Pa­tients should be educated to eliminate the most important risk factors for oral cancer (tobacco and alcohol), and to report in a timely manner any changes in signs or symp­toms of premalignant lesions.

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