|Year : 2021 | Volume
| Issue : 2 | Page : 43-48
Vocal fold leukoplakia: An experience of a tertiary care teaching hospital of Eastern India
Santosh Kumar Swain, Swaha Panda
Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
|Date of Submission||20-Jan-2021|
|Date of Decision||23-Feb-2021|
|Date of Acceptance||24-Jul-2021|
|Date of Web Publication||21-Aug-2021|
Santosh Kumar Swain
Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Background: Vocal fold leukoplakia (VFL) is a term used to document a white patch on the mucosa of the vocal folds. It is caused by prolonged use of smoking, consumption of alcohol, excessive drying, or voice abuse and is considered premalignant lesion of the larynx. Aim: The study aims to analyze the demographic and clinical parameters, pathological findings, and management of VFL patients, as well as the incidence of laryngeal cancer among these patients. Materials and Methods: We retrospectively collected 92 VFL patients who received treatment during November 2015 to December 2018 and followed up for a minimum period of 2 years up to December 2020. The detail clinical characteristics including endoscopic findings, postoperative pathological findings, and management were assessed from the patient's file. Results: The mean age of presentation was 64.3 years, with 52 male and 40 female patients. We found cigarette smoking as the most common etiological factor, which was seen in 45 patients (48.91%) followed by alcohol consumption and laryngopharyngeal reflux. Seventy-seven patients underwent surgery (42: carbon dioxide laser excision and 35: coblation-assisted excision), and rest 15 patients treated conservatively. On postoperative, the different pathological variants encountered were nondysplasia (n = 41); low-grade dysplasia (n = 24); high-grade dysplasia (n = 5); carcinoma in situ (n = 4); and invasive carcinoma (n = 3). Factors such as age (P < 0.001) and morphological types (P = 0.043) have been significantly correlated with pathological grades of VFL. Conclusion: The invasive laryngeal cancer detection rate underlying VFL at first diagnosis was 3.90%. The early diagnosis of VFL and treatment are challenge for clinicians to decrease the incidence of laryngeal malignancy. The patient's age and morphological types may guide treatment of VFL due to risk stratifications.
Keywords: Cigarette smoking, dysplasia, malignancy, vocal fold leukoplakia
|How to cite this article:|
Swain SK, Panda S. Vocal fold leukoplakia: An experience of a tertiary care teaching hospital of Eastern India. Oncol J India 2021;5:43-8
| Introduction|| |
Any pathological lesions in the vocal fold including vocal fold leukoplakia (VFL) result in hoarseness of the voice. VFL is clinically defined as white mucosal lesion of the vocal fold, which cannot be characterized as any other condition. It is broadly classified into keratosis with nondysplasia and keratosis with dysplasia. The laryngeal leukoplakia was first documented by Durant in 1880, and this entity was studied further in 1920 by Pierce and Jackson. Since then, the VFL has been considered to be a precancerous lesion of laryngeal malignancy. It has tendency for malignant transformation, so its early diagnosis is challenge for a clinician. Its occurrence and development are associated with long-standing effects of certain triggering factors, such as smoking and alcohol. The common clinical presentations of the VFL are hoarseness of voice, throat discomfort, and irritating cough. The benign and malignant lesions in the VFL cannot be discriminated on the basis of the clinical presentations and endoscopic pictures without performing biopsy.
The VFL presentation could range from benign variant of hyperplasia to invasive squamous cell carcinoma. The VFL is ideally treated individually on the basis of its benign or malignant possibility. However, it is need to determine the potential for malignant transformation of the benign and premalignant lesions to assess the importance of surgical intervention. The histopathological finding of dysplasia in VFL is an important prognostic factor for malignant transformation.
In the present retrospective study, we reviewed our experience on clinical presentations, etiopathological characteristics, and management strategies among the VFL patients who received treatment in our tertiary care institute and assessed the prognostic parameters among these patients.
| Materials and Methods|| |
Patients with a clinical diagnosis of the VFL those attending to the department of otorhinolaryngology of our tertiary care institute and received treatment during the period from November 2015 to December 2018 and followed up for a minimum period of 2 years up to December 2020 were enrolled in this study. This study was approved by the institutional ethical committee (via letter number: IEC/IMS/SOA/34). There were 92 patients of VFL participated in this retrospective study those identified as leukoplakia on the vocal fold at the department of otorhinolaryngology. All the procedures were done with involvement of human participants as per ethical standards of the institutional and national research committee and with 1964 Helsinki Declaration and its later amendments. Consents were obtained for surgical interventions from all the participants included in this study.
All the patients were diagnosed by laryngeal endoscope as white plaques on the vocal folds [Figure 1]. The clinical data including age, gender, laryngoscopic findings, surgical techniques, and postoperative outcome were documented. The preoperative laryngoscopic procedure was done to assess the morphological features, and based on laryngoscopic findings, VFL was classified into three morphological types, such as flat and smooth, elevated and smooth, and rough type.
Multiple or bilateral leukoplakia may coexist in vocal folds. Elevated and smooth VFL was considered if both elevated and smooth, and flat and smooth lesions of leukoplakia present in vocal folds. Rough leukoplakia was considered if rough lesions of leukoplakia present in vocal folds.
Patients diagnosed histopathologically as a case of laryngeal squamous cell carcinoma or patients previously who underwent laryngeal microsurgery or radiotherapy involving the neck or larynx due to any reason were excluded from this study. Any other laryngeal diseases which could appear as a white lesion of vocal fold such as laryngeal tuberculosis, laryngeal fungal infection, and upper respiratory tract infection were excluded from this study. The laryngeal tuberculosis and laryngeal fungal infections were excluded on the basis of the past histopathological diagnosis.
Surgery was performed in patients who gave consents for microlaryngeal surgery under general anesthesia. The microlaryngeal surgery was done under general anesthesia by endotracheal intubation and full exposure of the glottic lesions with a binocular microscope (ZEISS, S8, Carl Zeiss, Germany). An operating laryngoscope was placed into suspension, and the leukoplakic lesion of the vocal fold was completely excised by laser (Lumenis carbon dioxide [CO2] laser, New York) and coblation (Smith Nephew, Watford, United Kingdom). Complete resection of VFL was done by CO2 laser. In coblation technique, laryngeal wand was used to excise the leukoplakia of the vocal fold. Patients who had bilateral leukoplakia were treated with staged procedures. Hemostasis was achieved with topical application of cotton ball soaked with adrenaline (1:1000) (adrenaline injection contains epinephrine, strength 1 g/ml, manufactured by Maya Biotech, Chandigarh, India). The postoperative pathological types of leukoplakia lesions were classified on the basis of the World Health Organization 2005 guidelines such as squamous cell hyperplasia with nondysplasia, mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ (CIS), and squamous cell carcinoma. We considered mild dysplasia as low-grade dysplasia and moderate-to-severe dysplasia as high-grade dysplasia. The different histopathological findings were divided into two groups such as low risk which includes nondysplastic pathologies and low-grade dysplasia and high risk which includes high-grade dysplasia, CIS, and invasive cancers. The association of different factors with the histopathological findings for risk stratifications was calculated using Chi-square test. The association of the factors considered as significant if P < 0.05.
The postoperative follow-up was done every 3 months for the first 2 years. All postoperative patients were assessed by office-based rigid laryngoscope (Panasonic GP-KS822) examination. The nonsurgical treatment included cessation of the smoking and alcohol, strict voice rest, and proton pump inhibitor (omeprazole 20 mg twice daily for 6 weeks) in VFL associated with laryngopharyngeal reflux.
All the statistical analyses were done by using IBM Corporation, 2015,Chicago,Illinois, USA.
| Results|| |
The study population included 92 patients of VFL. The age range of the patients was from 28 to 74 years, with the mean age of 64.3 years. The male-to-female ratio was 1.3:1. The baseline clinical characteristics are presented in [Table 1]. The possible etiological factors encountered for VFL were tobacco addiction in the form of either cigarette smoking or alcohol consumption or both and laryngopharyngeal reflux. We found cigarette smoking as the most common etiological factor and seen in 45 patients (48.91%) followed by alcohol consumption and laryngopharyngeal reflux. The most common clinical presentation was hoarseness of voice (100%), followed by foreign body sensation in the throat and irritation in the throat. VFL lesions were unilateral in 69 patients and bilateral in 23 cases. As VFL patients with multiple lesions or bilateral lesions are considered as one morphological type according to higher degree of findings on endoscopy, we found 61 (66.30%) patients as smooth and flat, 20 (21.74%) as smooth and elevated, whereas 11 (11.96%) as rough types. All the smooth and elevated varieties and rough varieties of the leukoplakia were associated with exposure of cigarette smoking. There were only 14 patients of VFL with smooth and flat types exposed to cigarette smoking. Nineteen out of the 23 bilateral VFL patients were smooth and flat types of lesions, and rest four cases showed smooth and elevated types of leukoplakia.
|Table 1: Demographic and clinical profile of the patients with vocal fold leukoplakia|
Click here to view
Surgery was performed in 77 VFL cases whereas rest 15 (16.30%) patients avoided surgery and treated conservatively. Among surgery group, 42 (45.65%) patients underwent CO2 laser excision, and 35 (38.04%) underwent coblation-assisted excision of the VFL lesion. All the surgery performed patients underwent speech therapy. Based on the histopathological findings [Table 2], the operated patients (n = 77) were divided into two groups such as low risk (nondysplastic pathologies: N = 41; and low-grade dysplasia: N = 24) and high risk (high-grade dysplasia: N = 5; CIS: N = 4; and invasive cancers: N = 3). There was a significant association of age (P < 0.001) and morphological types (P = 0.043), with the postoperative histopathological grading of VFL lesions. 75% of high-risk VFL patients were seen in the age group of ≥50 years, whereas only 43.08% of low-risk patients were found in the age group ≥50 years. 25.55% of high-risk VFL patients were rough morphological type, whereas it was 6.15% for low-risk VFL patients [Table 3]. Invasive cancer underlying VFL at initial diagnosis was 3.90% (3 out of 77 postoperative histological analysis). The cases of invasive cancers referred for radiotherapy. All three cases of invasive carcinoma were found in male sexes and above the age of 50 years with past history of addiction to the cigarette smoking. All these invasive carcinomas were found in one vocal fold only.
|Table 2: Histopathological findings in operated cases of vocal fold leukoplakia (n=77)|
Click here to view
|Table 3: The association of clinical characteristics with findings on postoperative pathology|
Click here to view
All the cases of VFL attended a minimum 2-year follow-up and the median follow-up period was 26 months. There were no malignant transformations in any patients during follow-up period. Out of 92 cases, 5 (5.43%) cases still revealed the residual leukoplakia lesion in the vocal folds at 1-year follow-up (4 rough types and 1 smooth and elevated type). Four residual lesions found in patients who had taken conservative treatment, and rest one residual lesion found in surgery group who underwent coblation-assisted excision of the VFL. These four residual lesions after conservative approach appear less severity morphologically on endoscopy. Among these five cases with residual lesion, three cases underwent surgical excision and two cases were treated conservatively.
| Discussion|| |
It is important to identify VFL patients who are at high risk for cancer development to offer a more aggressive treatment for controlling laryngeal cancer. The degree of the dysplasia or depth of the lesions of the vocal fold cannot be established only on the basis of the laryngoscopic examination; biopsy is needed to diagnose keratosis with dysplasia or malignancy or to confirm that a keratosis is benign lesion. We retrospectively reviewed our institutional experience on VFL patients to analyze etiopathological parameters, underlying invasive carcinoma at diagnosis, and outcomes of treatment modalities.
The prolonged use of the tobacco and alcohol, gastroesophageal reflux, occupational hazards (e.g., asbestos), nutritional deficiencies, vocal abuse, chronic infections, and hormonal disorders are presumed to be etiological agents for the development VFL.,, Especially, tobacco use in the form of cigarette smoking is considered as a major risk factor toward the development of the VFL and laryngeal malignancy. We found 48.91% of VFL patients having habit of cigarette smoking.
The VFL is a clinical diagnosis which describes a whitish patch or a plaque on the vocal fold/glottis. The laryngoscopic examination is an important tool for clinical diagnosis of VFL by direct inspection of the larynx. Advanced endoscopic tools, narrow band imaging (NBI), optical coherence tomography, and contact endoscope have been introduced to improve the detection of the VFL. The ability of the flexible or rigid laryngoscopy to assess the lesions of the vocal folds continues to improve. White light (WL) and NBI laryngoscopy together are better for accurate diagnosis of the VFL. Laryngoscopic examination under WL displays the lesion more directly and clearly. NBI endoscopy is useful for distinguishing between the benign and malignant types of the VFL, and it highlights vascularization of the lesion. Stroboscopic examination is helpful for determining the progressive thickness of the vocal fold epithelium. The leukoplakia at the medial border of the vocal folds is better visualized by stroboscopy than flexible laryngoscopy. We used office laryngoscopes for precise identification of the surface, margin, texture, and size of the lesion.
VFL encompasses a variety of lesions from benign to premalignant and malignant lesions. At present, there is no standard classification for VFL because of limited morphological characteristics, which hampers the establishment for standard treatment of VFL. Few reports clinically classified VFL into three morphological types such as superficial, exophytic, and ulcerative types. The morphological criteria for such categorization of VFL are thickness, texture, size, hyperemia, and symmetry. Similar to Chen et al., we clinically classified VFL into flat and smooth type, elevated and smooth type, and rough type. In our study, majority of VFLs were smooth and flat types (66.30%), whereas Chen et al. found rough type as the most common finding (52.3%). Histopathological examination of the VFL is an accepted method for diagnosis. Pathologically, VFL can be squamous hyperplasia with or without keratosis, epithelial dysplasia of various grades of severity, CIS, or invasive carcinoma., In our study, majority of cases were pathologically low-risk type which consisted of nondysplastic lesions (53.25%) and low-grade dysplasia (31.17%). Rest 15.58% of patients were of high-risk types consisting high-grade dysplasia, CIS, and invasive carcinoma. Moreover, our data were supported by several literatures. Isenberg et al., Cui et al., Yang et al., and Zhu et al. in their studies found that 53%, 54.2%, 54.5%, and 61.6% of VFL cases, respectively, were nondysplastic lesions. However, Chen et al. in a study found lower rate on nondysplasia (10.4%) among VFL patients and they suggested that different treatment strategies for the three morphological types of VFL could be the possible explanation for such lower rate of nondysplasia. These nondysplasia patients did not require unnecessary surgical treatment and should be managed as close observation or conservative treatment unless otherwise found ineffective. However, prompt surgical treatment was required for patients with rough-type VFL due to increased rate of detection of high-grade dysplasia and malignancy among these.
The macroscopic pictures of VFL have been related with pathological changes. Based on macroscopic features, the morphological types flat and smooth, elevated and smooth, and rough type are staged into initial, middle, and advanced stages, respectively. As the stages increased, the nondysplasia rate decreases, whereas the proportion of cancer gradually increases. Chen et al. found a significant correlation between morphological types/stages of VFL with pathological grades of VFL (P < 0.001). They found that the incidence of nondysplasia was 68% in flat and smooth, 13% in elevated and smooth, and 1% in rough type of leukoplakia lesions; however, the incidence of carcinoma was 0% in flat and smooth, 5.2% in elevated and smooth, and 30.6% in rough type of leukoplakia lesions. In the present study, all the three invasive cancer cases were of rough morphological type. Hence, the incidence of invasive carcinoma was 0% in flat and smooth, 0% in smooth and elevated, and 27.3% in rough type of VFL lesions.
VFL is merely a clinical diagnosis without any histological or prognostic implications. Hence, it is important to keep in mind that a certain percentage of VFL already contains carcinoma at initial diagnosis of VFL. At the meantime, secondary malignant transformation rates in VFL patients are also important. The malignant transformation rates among VFL patients with no dysplasia, mild-to-severe dysplasia, and CIS proportionally increase., The association of VFL with laryngeal carcinoma is the important focus of several clinical studies on VFL. Bouquot et al. in a population-based study detected 12% of invasive cancer rate underlying leukoplakia at first diagnosis. In the present study, the invasive cancer detection rate in underlying VFL patients at first diagnosis was 3.90% (3 out of 77 pathologically analyzed cases). Studies suggested that the clinical diagnosis of the leukoplakia is associated with a 6%–7% of the cases progress to carcinoma.
Smoking is an important risk factor for malignant transformation. Both the increased duration of cigarette smoking and the amount of cigarette smoking have been associated with higher chance of malignant transformation., Moreover, alcohol drinking associated positively for development of the laryngeal malignancy. All the three diagnosed invasive carcinoma among VFL patients were associated with cigarette smoking. A study by Kostev et al. on 1184 vocal cord leukoplakia patients from a large nationwide practice database in Germany revealed that vocal cord leukoplakia has increased risk for malignancy with advanced age and male sex. In our study, all the three diagnosed cases of invasive carcinoma among VFL patients were found in male sexes and above the age of 50 years.
There is still no consensus on the treatment of VFL patients. Surgical and nonsurgical conservative treatments are the options for managing the VFL. Complete surgical excision of the lesion is the recommended treatment because of the potentiality of its malignant transformation and also gives a histopathological diagnosis. Till date, surgical excision is done in majority of cases before getting the histopathological diagnosis. Several leukoplakia lesions with nondysplasia which does not convey the premalignant potential receive unnecessary surgical treatment in routine clinical practice. There are few reports regarding nonsurgical treatment for VFL. In this study, 16.30% of cases underwent nonsurgical treatment. CO2 laser is an ideal surgical procedure for VFL and is also an important tool for performing cordectomy in vocal fold malignancy., The outcome of the laser surgery is dependent on the skill of the surgeon and his/her abilities with cold steel microsurgical instruments. The overtreatment of the VFL may result scars of the vocal fold and cause voice deterioration. Coblation is a minimally invasive low heat-producing technique, which delivers plasma layer for dissolution of the target tissues. In this study, 45.65% of cases underwent laser excision of the VFL, whereas 38.04% of cases underwent coblation-assisted excision of the VFL. The speech rehabilitation or therapy is an important measure after excision of the leukoplakia. It includes vocal hygiene and educating the patient for voice conservation. The patient is advised to avoid voice abuse, repetitive throat clearing, and other vocal fold irritants. Products causing dehydration of the mucosa of the vocal folds including smoking, alcohol, and antihistamines should be avoided by the patients. Adequate fluid intake should be ensured to counter dehydrations.
The preventive measures such as cessation of smoking, alcohol, phonotrauma, treatment of laryngopharyngeal reflux, and avoidance of industrial pollutants should be taken to decrease the incidence of VFL and consequence laryngeal malignancy.
| Conclusion|| |
VFL corresponds to variety of the pathologies from benign keratosis to dysplastic lesion and CIS to squamous cell carcinoma. Complete excision of the lesions can be safely done by laser or coblation. Preventive measures such as cessation of smoking, alcohol abuse and phonotrauma, and adequate treatment of the laryngopharyngeal reflux should be taken to decrease the incidence of VFL-induced laryngeal cancer. Careful preoperative identification of VFL with possible different type of pathologies from nondysplastic to dysplastic lesion is important to avoid unnecessary surgery-induced morbidity for nondysplastic lesions and at the mean time to go for prompt surgical interventions for dysplastic lesions. Hence, further evaluation with large-scale prospective studies is necessary.
There are some limitations of the present study. At first, it is retrospective nature and a single center-based study. Postsurgical voice assessment for both the CO2 laser excision and coblation surgical procedures was not done for comparison. Follow-up duration is short to observe for malignant transformation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Swain SK, Behera IC, Sahoo L. Hoarseness of voice in the pediatric age group: Our experiences at an Indian teaching hospital. Indian J Child Health 2019;6:674-8.
Panwar A, Lindau R 3rd
, Wieland A. Management of premalignant lesions of the larynx. Expert Rev Anticancer Ther 2013;13:1045-51.
Pierce NH. Leukoplakia laryngis. Ann Otol Rhinol Laryngol 1920; 29:24.
Park YM, Jo KH, Hong HJ, Choi HS. Phonatory outcome of 585 nm/pulsed-dye laser in the management of glottic leukoplakia. Auris Nasus Larynx 2014;41:459-63.
Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36:575-80.
Cui W, Xu W, Yang Q, Hu R. Clinicopathological parameters associated with histological background and recurrence after surgical intervention of vocal cord leukoplakia. Medicine (Baltimore) 2017;96:e7033.
Lee DH, Yoon TM, Lee JK, Lim SC. Predictive factors of recurrence and malignant transformation in vocal cord leukoplakia. Eur Arch Otorhinolaryngol 2015;272:1719-24.
Thompson L. World Health Organization classification of tumours: Pathology and genetics of head and neck tumours. Ear Nose Throat J 2006;85:74.
Villa A, Wook SB. Leukoplakia – A diagnostic and management algorithm. J Oral Maxillofacial Surg 2017;75:723-34.
Kostev K, Jacob LE, Kalder M, Sesterhenn AM, Seidel DU. Association of laryngeal cancer with vocal cord leukoplakia and associated risk factors in 1,184 patients diagnosed in otorhinolaryngology practices in Germany. Mol Clin Oncol 2018;8:689-93.
Gale N, Michaels L, Luzar B, Poljak M, Zidar N, Fischinger J, et al.
Current review on squamous intraepithelial lesions of the larynx. Histopathology 2009;54:639-56.
Swain SK, Behera IC, Mohanty JN. Laryngeal manifestations due to smoking among the pediatric age group-our experiences at an Indian teaching hospital. Arch Med Health Sci 2019;7:186. [Full text]
Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, et al.
Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe. Am J Epidemiol 2007;165:814-20.
Zhukhovitskaya A, Battaglia D, Khosla SM, Murry T, Sulica L. Gender and age in benign vocal fold lesions. Laryngoscope 2015;125:191-6.
Chen M, Li C, Yang Y, Cheng L, Wu H. A morphological classification for vocal fold leukoplakia. Braz J Otorhinolaryngol 2019;85:588-96.
Staníková L, Šatanková J, Kučová H, Walderová R, Zeleník K, Komínek P. The role of narrow-band imaging (NBI) endoscopy in optical biopsy of vocal cord leukoplakia. Eur Arch Otorhinolaryngol 2017;274:355-9.
Djukic V, Milovanovic J, Jotic AD, Vukasinovic M. Stroboscopy in detection of laryngeal dysplasia effectiveness and limitations. J Voice 2014;28:262.e13-21.
Swain SK, Choudhury J. Pediatric airway diseases. Indian J Health Sci Biomed Res (KLEU) 2019;12:196-201.
Fang TJ, Lin WN, Lee LY, Young CK, Lee LA, Chang KP, et al.
Classification of vocal fold leukoplakia by clinical scoring. Head Neck 2016;38 Suppl 1:E1998-2003.
Isenberg JS, Crozier DL, Dailey SH. Institutional and comprehensive review of laryngeal leukoplakia. Ann Otol Rhinol Laryngol 2008;117:74-9.
Yang SW, Chao WC, Lee YS, Chang LC, Hsieh TY, Chen TA, et al.
Treatment outcome of vocal cord leukoplakia by transoral laser microsurgery. Lasers Med Sci 2017;32:19-27.
Zhu H, Xu W, Li Y, Cheng L. Observation of clinicopathological characteristics of vocal fold leukoplakia and laryngopharyngeal reflux. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2014;49:368-73.
Gale N, Gnepp DR, Poljak M, Strojan P, Cardesa A, Helliwell T, et al.
Laryngeal squamous intraepithelial lesions: An updated review on etiology, classification, molecular changes, and treat-ment. Adv Anat Pathol 2016;23:84-91.
Bouquot JE, Kurland LT, Weiland LH. Laryngeal keratosis and carcinoma in the Rochester, MN, population 1935-1984. Cancer Detect Prev 1991;15:83-91.
Montgomery J, White A. A decade of laryngeal leukoplakia in Paisley, Scotland. Eur Arch Otorhinolaryngol 2012;269:947-51.
van Hulst AM, Kroon W, van der Linden ES, Nagtzaam L, Ottenhof SR, Wegner I, et al.
Grade of dysplasia and malignant transformation in adults with premalignant laryngeal lesions. Head Neck 2016;38 Suppl 1:E2284-90.
Karatayli-Ozgursoy S, Pacheco-Lopez P, Hillel AT, Best SR, Bishop JA, Akst LM. Laryngeal dysplasia, demographics, and treat-ment: A single-institution, 20-year review. JAMA Otolaryngol Head Neck Surg 2015;141:313-8.
Swain SK, Behera IC, Sahoo L. Pediatric Laryngeal papillomatosis: Experiences at an Indian teaching hospital. J Health Res Rev 2019;6:114-21. [Full text]
Benninger MS. Microdissection or microspot CO2 laser for limited vocal fold benign lesions: A prospective randomized trial. Laryngoscope 2000;110:1-17.
Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ. Human papilloma virus and head and neck cancer: A systematic review and meta-analysis. Clin Otolaryngol 2006;31:259-66.
[Table 1], [Table 2], [Table 3]