Epidemiology of Head & Neck Precancer

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Prevalence rates (per 1,000 adults) for oral leukoplakia in U.S. and European populations.

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How Common are Oral Precancers?

Incidence rates. No Western study has determined incidence for oral leukoplakia, although in India new lesions have been shown to occur in 0.8/1,000,000 persons annual, compared to an oral cancer incidence rate in the same population of 5/1,000,000. It is not known or assumed that all oral cancers in India arise from leukoplakic lesions, but a large proportion of them probably do so. In the U.S., Bouquot et al attempted to determine the leukoplakia incidence in the predominantly white community in which the Mayo Clinic resides, but were unable to do so because data from local dentists could not be compiled.

Likewise, no good incidence data are available for oral erythroplakia, but incidence investigations of oral/pharyngeal carcinoma in situ, which represents the vast majority of erythroplakias, have determined that only six cases are diagnosed per one million persons each year.

The only other head and neck precancerous lesions for which epidemiologic data are available are laryngeal keratosis (leukoplakia of vocal cords) and laryngeal carcinoma in situ. These lesions are diagnosed annually in 5.8 and 0.4 persons per 100,000 population.

Prevalence Rates. Since the 1950s a number of reports have indicated that at least the most common form of oral premalignancy, leukoplakia, is quite common indeed (Table 2), and that it represents one of the five most common chronic diseases affecting the oral mucosa. More recent studies have been especially careful to eliminate frictional keratosis and smokeless tobacco keratosis from their collections of true leukoplakia, and so the prevalence has been reduced somewhat from 3-4% of an adult Western population to 1-2%. Even at 1% of the adult population, however, it can be estimated that 1,800,000 Americans are afflicted with this premalignancy.

Smokeless tobacco keratosis has a much lower malignant transformation potential than leukoplakia, but in some populations where the habit of chewing tobacco is popular, lesions can be found in up to 9% of males.

Oral lichen planus, a questionable precancer, affects one of every 1,000 adults in Western populations; in certain subpopulations it is seen as often as once per 32 persons.

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Are Some Worse Than Others?

Predicting the risk of malignant transformation of any particular precancer of the head and neck region is a formidable task.  The tremendous number of potential influencing factors and cofactors, along with great differences in study design and disease definitions, has led to considerable confusion on this subject.  Nevertheless, it is important to at least make the effort to establish or estimate relative risk, and to this end the following table provides a "best guess" relative risk for the various types of oral precancers.

Table 1: Estimated relative risk of developing oral cancer from various oral precancers.

Reference: Modified from: Bouquot JE. The pathology and progression of oral premalignancy. Proceedings, Epithelial Dysplasia Symposium, 5th International Congress on Oral Cancer, Royal College of Physicians, London, United Kingdom; September, 1997.

Disease Name

Malignant Transformation Potential
Proliferative verrucous leukoplakia (PVC) ******
Nicotine palatinus in reverse smokers # ******
Erythroplakia *****
Oral submucous fibrosis *****
Erythroleukoplakia ****
Granular (verruciform, rough) leukoplakia ****
Laryngeal keratosis (leukoplakia) ***
Actinic cheilosis ***
Smooth, thick leukoplakia **
Lichen planus (erosive forms) **
Smooth, red tongue of Plummer-Vinson disease **
Smokeless tobacco keratosis *
Smooth, thin leukoplakia +/-
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  # reverse smoking: smoking with the lit end of the cigarette in one's mouth


 

Tables for Specific Precancers

Click on table number (if underlined) to see data for specific lesions.

Table 2 Leukoplakia
Table 3 Erythroplakia
Table 4 Carcinoma in situ
Table 5 Laryngeal Keratosis
Table 6 Lichen Planus
Table 7 Smokeless Tobacco Keratosis
Table 8 Other Oral Mucosal Lesions
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Table 2: Prevalence rates (per 1,000 persons) for oral leukoplakia, listed by date of publication. 


References are at end of this page, listed by date of publication.

Author(s)

Year

Country

Average Age

Population
Size

Rural/Urban

#
Leukoplakia

# per
1,000

Gerry, et al.

1952

Guatemala

2,004

Rural

8

4

Mehta, et al

1961

India

4,734

Urban

166

35

Bruszt

1962

Hungary

all

5,613

Urban

202

36

Atkinson, et al.

1964

New Guinea

3,996

Rural

324

81

Pindborg, et al

1965

India

n/a

10,000

Both

150

33

Forlen, et al.

1965

New Guinea

753

Rural

128

170

Pindborg, et al

1966

India

n/a

20,000

Both

328

15

Zachariah,et al

1966

India

n/a

5,000

Rural

118

24

Pindborg, et al

1968

New Guinea

>20

1,266

Rural

56

46

Banoczy, et al.

1969

Hungary

16,322

Rural

98

06

Jussawala, Rajpal

1969

India

40,000

Rural

2,800

70

Mehta, et al

1969

India

>15

50,915

Rural

881

17

Wahi, Mital

1970

India

7,286

Rural

379

52

Chrigstrom

1970

Sweden

>18

201

Urban

6

30

Gangadarhan, Paymaster

1971

India

all

203,249

Urban

1,422

7

Knapp

1971

U.S.A.

18-25

181,338

Both

363

2

Ross, Gross

1971

U.S.A.

>18

11,884

Urban

380

32

Mehta, et al

1972

India

>15

101,761

Rural

685

7

Sonkodi, Toth

1973

Hungary

1,071

Urban

13

12

Srivastava

1973

India

>18

8,428

Rural

236

28

Grabowski

1974

Denmark

>65

557

Rural

7

13

Silverman, et al.

1976

India

57,518

Urban

2,071

36

Axell

1976

Sweden

>15

20,333

Urban

717

36

Wilsch, et al

1978

Germany

4,000

Urban

88

22

Lay, et al

1982

Burma

>15

6,000

Rural

101

17

Zhang Kui-Hua

1983

China

134,492

Rural

14,122

105

Rodriquez, et al

1983

Cuba

>20

749

Urban

16

21

Zachariah, Pindborg

1985

India

all

152,676

Rural

3,053

2-30

Zachariah, Pindborg

1985

India

all

24,000

Urban

480

20

Bouquot, Gorlin

1986

U.S.A.

>35

23,616

Both

682

29

Reichart, et al

1987

Thailand

all

1,866

Rural

21

11

Hogewind, van der Waal

1988

Netherlands

all

1,000

Urban

14

14

Banoczy, Rigo

1991

Hungary

all

7,820

Rural

104

13

Ikeda, et al

1991

Japan

all

3,131

Urban

77

25

Ikeda, et al

1995

Cambodia

>15

1,319

Urban

14

11

Prout, et al

1997

U.S.A.

>40

4,511

Urban

28

6


 

Table 3: Prevalence rates (per 1,000 persons) for erythroplakia of the oral mucosa.

References are at end of this page, listed by date of publication.

Author(s) Year Country Population Size # Cases
per 1,000 Persons
Prout, et al

1997

USA

5,000

0.2   

Diaz-Guzman, Castellanos

1991

Mexico

8,000

1.9 * 

* 3.0/1,000 males; 1.4/1,000 females



Table 4
: Average annual incidence rates (per 100,000 persons/year) for
carcinoma in situ of various head and neck anatomic sites.
Population base: males = 900,312 person-years; females = 1,102,916 person-years).

Reference: Bouquot JE, Kurland LT, Weiland LH. Carcinoma in situ of the upper aerodigestive tract: incidence, time trends and follow-up in Rochester, Minnesota, 1935_1984. Cancer 1988; 61:1691-1698.

Anatomic site # New Cases/100,000/Person-Year
Males Females Total
Lip vermilion

2.0 (1.4)*

0.2 (0.2)* 

1.0 (0.8)*

Oral cavity

1.0 (0.6)

0.3 (0.3)

0.6 (0.4)

Pharynx 

0.7 (0.3)

0.1 (0.1)

0.4 (0.2)

Larynx 

0.8 (0.7)

 0.1 (0.1)

 0.4 (0.4)

Nasal/Paranasal Sinuses

 0.1 (0.1) 

0.0 (0.0)

 0.1 (0.1)

Total:

4.6 (3.1) 

0.6 (0.6)

 2.4 (1.8)


 

Table 5: Average annual incidence rates (per 100,000 persons/year) for laryngeal keratosis (leukoplakia), carcinoma in situ and invasive carcinoma of the larynx. Population base: males = 900,312 person-years; females = 1,102,916 person-years).

References: Bouquot JE, Weiland LH, Kurland LT. Laryngeal keratosis and carcinoma in the Rochester, Minnesota population, 1935-1984. Cancer Detect Prevent 1991; 15:83-91. Bouquot JE, Gnepp DR. Laryngeal precancer -- a review of the literature, commentary and comparison with oral leukoplakia. Head Neck 1991; 13: 488-497.

Diagnosis # New Cases/100,000 Person-Year
Males Females Total
Keratosis (leukoplakia) 10.2 2.1 5.8
Carcinoma in situ 0.7 0.1 0.4
Invasive carcinoma 7.0 0.3 3.3

 

Table 8: Gender-specific prevalence rates for all mucosal, soft tissue and bony oral and oropharyngeal lesions clinically diagnosed in 23,616 white U.S. adults (97% whites; 8,477 males, 15,139 females) over 35 years of age, ranked by total prevalence. 

References: Modified and extended from Dr. Bouquot's earlier published papers.

Diagnosis

    # Lesions/1,000 persons

Male

Female

Total

Leukoplakia 42.47 13.14 23.67
Lesion, NOS, oral 23.48 17.64 19.73
Torus palatinus 13.21 21.73 18.67
Irritation fibroma 12.98 11.36 11.94
Fordyce granules 17.69 5.15 9.65
Torus mandibularis 9.56 7.86 8.47
Lesion, NOS, other 3.54 6.94 5.72
Hemangioma, oral 8.38 4.10 5.63
Inflammatory ulcer 5.43 5.09 5.21
Inflammatory erythema, oral 4.48 4.76 4.66
Papilloma 5.31 4.16 4.57
Epulis fissuratum 3.42 4.36 4.02
Varicosities 3.54 3.43 3.47
Fissured tongue 3.54 3.10 3.26
Inflammatory erythema, oropharynx 3.54 2.97 3.18
Geographic tongue 3.42 2.97 3.13
Trauma, NOS, oral 2.95 3.24 3.13
Papillary hyperplasia 1.65 3.77 3.01
Herpes labialis 2.36 2.64 2.54
Mucocele 1.89 2.64 2.37
Scar tissue 2.36 1.92 2.07
Angular cheilitis 1.77 1.85 1.82
Hyperplastic lingual tonsil 2.36 1.19 1.61
Hematoma/echhymosis 2.01 1.39 1.61
Frictional keratosis (cheek bite) 0.71 1.39 1.14
Hyperplastic pharyngeal tonsil 1.53 0.86 1.10
Lichen planus 1.18 1.06 1.10
Smokeless tobacco keratosis 2.71 0.07 1.02
Buccal exostosis 0.94 0.86 0.89
Leaf-shaped fibroma (beneath denture) 0.35 1.19 0.89
Amalgam tattoo 0.59 0.99 0.85
Median rhomboid glossitis 0.83 0.53 0.64
Hairy tongue (black) 1.18 0.26 0.59
Glossitis, atrophic 0.59 0.53 0.55
Epidermoid cyst 0.71 0.40 0.51
Nevocellular nevus, oral 0.12 0.66 0.47
Leukoedema 0.83 0.13 0.38
Oral melanotic macule 0.47 0.33 0.38
Non-lingual oral tonsils, hyperplastic 0.47 0.33 0.38
Nicotine palatinus 0.59 0.13 0.30
Herpes zoster, intraoral 0.47 0.20 0.30
Lipoma 0.12 0.40 0.30
Pseudomembranous candidiasis 0.35 0.20 0.25
Ranula 0.12 0.33 0.25
Herpes simplex, intraoral 0.12 0.26 0.21
Sialolithiasis 0.00 0.26 0.17
Bifid uvula 0.35 0.00 0.13
White coated tongue 0.35 0.00 0.13
Gingival hyperplasia 0.12 0.13 0.13
Hyperplastic buccinator node 0.12 0.07 0.08
Commissural lip pits 0.12 0.07 0.08
Cyst of Blandin-Nuhn 0.00 0.13 0.08
Basal cell carcinoma, vermilion 0.12 0.00 0.04
Macroglossia 0.00 0.07 0.04
Pyogenic granuloma 0.00 0.07 0.04
Nasoalveolar cyst 0.00 0.07 0.04
Neurofibroma 0.00 0.07 0.00

Diagnoses of biopsied oral leukoplakias:

Hyperkeratosis without dysplasia 9.67 3.30 5.59
Severe epithelial dysplasia 2.36 0.33 1.06
Squamous cell carcinoma I 2.71 0.07 1.02
Clinical Diagnosis, Face/Neck Lesions:
Lesion, NOS, face/neck * 11.09 9.78 10.25
Nevocellular nevus, face/neck 5.66 6.61 6.27
Actinic keratosis, face/neck 3.66 4.03 3.90
Cervical adenopathy, inflammatory 3.07 4.03 3.68
Enlarged thyroid gland 0.47 3.17 2.20
Basal cell carcinoma, face 3.19 1.65 2.20
Seborrheic keratosis, face/neck 1.53 1.39 1.44
Lipoma, face/neck 1.42 0.99 1.14
Sebaceous cyst, face/neck 1.65 0.79 1.10
Verruca vulgaris, face/neck 1.30 0.46 0.76
Hemangioma, face 0.59 0.33 0.42
Xanthoma/xanthelasma, face 0.24 0.20 0.21
Osteoma, facial bones/skull 0.12 0.13 0.13
Thyroglossal duct cyst, neck 0.24 0.00 0.08
Nasal polyp 0.12 0.00 0.04
Malignant melanoma, face

0.00

0.07 0.04
Butterfly rash of lupus 0.00 0.07 0.04
History of Oral Cancer:
No lesion, history of oral cancer 2.40 0.73 1.31
No lesion, family history of oral cancer 3.64 2.51 2.89
Oral carcinoma, history of previous oral cancer 0.51 0.00 0.18
Oral leukoplakia, history of previous oral carcinoma 1.37 0.18 0.59
Table of Specific Lesions  Top of This Page

* NOS = not otherwise specified; all cases biopsy proven and included in leukoplakia rates, except the single case of basal cell carcinoma of the vermilion border.


References, Dr. Bouquot's Prevalence Data

Bouquot JE. An Epidemiologic Evaluation of Oral Carcinoma, Premalignant Epithelial Dysplasia and Nonspecific Clinical Keratoses in an Adult Minnesota Population of 23,616. Master's Thesis, University of Minnesota Graduate School, 1974, pp 1-96.

Bouquot JE. Common oral lesions found during a mass screening examination. J Amer Dent Assoc 112:50-57, 1986.

Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus and other oral keratoses in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 61:373-381.

Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 62:284-291.

Bouquot JE, Gundlach KKH. Odd tongues: the prevalence of common tongue lesions in 23,616 white Americans over 35 years of age. Quint Internat 1986; 17:719-730.

Bouquot JE. Epidemiology. In: Gnepp DG. Pathology of the head and neck. New York: Churchill Livingstone, 1987, pp 263-314.

Bouquot JE, Gundlach KKH. Odd lips: the prevalence of common lip lesions in 23,616 white Americans over 35 years of age. Quint Internat 1987; 18:277-284.

Bouquot JE, Crout RJ. Odd gums: The prevalence of common gingival and alveolar lesions in 23,616 white Americans over 35 years of age. Quint Internat 1988; 19:747-753.

Table of Specific Lesions  Additional Epidemiologic Studies by Dr. Bouquot  Top of This Page

References: Epidemiology of Oral Premalignancy 
(including Carcinoma in Situ)

Note: Click on underlined author(s)'s name to see abstract, summary or full paper

Gerry RG, Smith ST, Calton ML. The oral characteristics of Guamians including the effects of betel chewing on the oral tissues. Oral Surg Oral Med Oral Pathol 1952; 5:762-781.

Banczy J, Radnai T, Remenyi I. Modszertani tapasztalataink Dunakesze es Felsogod, lakossagan vegzett stomatoonkologiai szurovizsgalatok alapjan. Fogorb Sz 1962; 62:118-122.

Atkinson L, Chester IC, Smith FG, et al. Oral cancer in New Guinea: a study in demography and etiology. Cancer 1964; 17:1289-1298.

Forlen HP, Hornstein O, Stuttgen G. Betelkauen und Leukiplakie. Arch Klin Exper Dermatol 1965; 221:463-480.

Pindborg JJ, Chawla TN, Misra RK, et al. Frequency of oral carcinoma, leukoplakia, leukoedema, leukokeratosis, submucous fibrosis and lichen planus in 10,000 Indians in Lucknow, Uttar Pradesh, India. J Dent Res 1965; 44:615-618.

Pindborg JJ, Kalapessi HK, Kale SA, et al. Frequency of oral leukoplakias and related diseases among 10,000 Bombayites. J All India Dent Assoc 1965; 37:1-2.

Bruszt P. Stomato-onkologische Reihenuntersuchungen in seiben Gemeinden Sudungarns. Schweiz Monatsschr Zahnheilkd 1966; 72:758-766.

Zachariah J, Matthew B, Varma NAR, et al. Frequency of oral mucosal lesions among 5,000 individuals in Trivandrum, South India. J All India Dent Assoc 1966; 38:290-294.

Pindborg JJ, Rhatt M, Devanath KR, et al. Frequency of oral white lesions among 10,000 individuals in Bangalore, South India. Indian J Med Sci 1966; 20:349-352.

Pindborg JJ, Barmes OD, Roed-Petersen B. Epidemiology and histology of oral leukoplakia and leukoedema among Papuans and New Guineans. Cancer 1968; 22:379-384.

Jussawala DJ, Rajpal RN. Leukoplakia: Proceedings of the symposium on precancer. Bulletin #39, New Dehli: National Inst Science India 1969:19-27.

Mehta FS, Pindborg JJ, Gupta PC, et al. Epidemiologic and histologic study of oral cancer and leukoplakia among 50,915 villagers in India. 1969; 24:832-849.

Wahi PN, Mital VP. Epidemiological study of precancerous lesions of the oral cavity: a preliminary report. Indian J Med Res 1970; 58:1361-1491.

Bouquot JE. An Epidemiologic Evaluation of Oral Carcinoma, Premalignant Epithelial Dysplasia and Nonspecific Clinical Keratoses in an Adult Minnesota Population of 23,616. Master's Thesis, University of Minnesota Graduate School, 1974, pp 1-96.

Sonkodi TK. Szegedi textitipari munkasok stomato-onkologiai vizgalata. Fogorv Sz 1974; 67:165-169.

Axéll T. The relation of the clinical picture to the histopathology of snuff dipper's lesions in a Swedish population. J Oral Path 1976; 5:229-236.

Mehta FS, Pindborg JJ, Bhonsle RB, Sinor PN. Incidence of oral leukoplakia among 20,358 Indian villagers in a 7-year period. Br J Cancer 1976; 33:549-554.

Silverman S, Bhargava K, Mani N, et al. Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujaret, India. Cancer 1976; 38:1790-1795.

Wilsch L, Hornstein OP, Bruning H, et al. Orale Leukopkein II. Ergebnisse einer 1 jahrigen poliklinischen Pilotstudie. Dtsch Zahnarztl Z 1978; 33:132-142.

Gupta PC, Mehta FS, Daftary DK, et al. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 1980; 8:287-333.

Winn DM, Blot WJ, Shy CM, et al. Snuff dipping and oral cancer among women in the southern United States. New Eng J Med 1981; 304:745-749.

Lay KM, Sein K, Myint A, et al. Epidemiologic study of 6,000 villagers of oral precancerous lesions in Bihigynn: preliminary report. Community Dent Oral Epidemiol 1982; 10:152-155.

Zachariah J, Pindborg JJ. Unpublished material as quoted in Pindborg JJ. Oral precancer. In: Barnes L (ed). Surgical pathology of the head and neck. New York: Marcel Dekker, 1985:279-331.

Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus and other oral keratoses in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 61:373-381.

Axell T. Occurrence of leukoplakia and some other oral white lesions among 20333 adult Swedish people. Community Dent Oral Epidemiol 1987; 15:46-51.

Bouquot JE. Epidemiology. In: Gnepp DR (ed). Pathology of the head and neck. Philadelphia: Churchill-Livingstone; 1988: 263-314.

Bouquot JE, Weiland LH, Kurland LT. Leukoplakia and carcinoma in situ synchronously associated with invasive oral/pharyngeal carcinoma in Rochester, Minnesota, 1935-1984. Oral Surg Oral Med Oral Pathol 1988; 65:199-207.

Bouquot JE, Gnepp D. Epidemiology of carcinoma in situ of the upper aerodigestive tract. Cancer 1988; 61:1685-1690.

Bouquot JE, Kurland LT, Weiland LH. Carcinoma in situ of the upper aerodigestive tract: incidence, time trends and follow-up in Rochester, Minnesota, 1935-1984. Cancer 1988; 61:1691-1698.

Bouquot J, Weiland L, Ballard D, Kurland L. Leukoplakia of the mouth and pharynx in Rochester, MN, 1935-1984; incidence, clinical features and follow-up of 463 patients from a relatively unbiased patient pool. J Oral Path 1988; 17:436.

Hogewind WFC. Oral leukoplakia in a Dutch population; a clinical study. Thesis. Amsterdam: Vrije Universiteit te Amsterdam, 1990:1-175.

Table of Specific Lesions  Top of This Page