Quick Review for Patients






Note: click on underlined words for more detail or photos.

A smokeless tobacco etiology for oral cancer was first suggested by James Ewing, who noted that cancer in the mouths of tobacco chewers most often developed at the site of quid placement. Ewing's premise was reiterated in Western clinicopathologic reports published during the 1940s, with specific reference to verrucous carcinoma. The high relative frequency of oral cancer (all types) in India, moreover, had focused attention on the causative role of chewing tobacco as early as 1908, when it was determined that an amazing 71-92% of all carcinomas diagnosed in hospital outpatients arose from the oral mucosa.

Verrucous carcinoma, a low-grade variant of squamous cell carcinoma, is so closely aligned with the use of snuff and chewing tobacco that it has been called the "snuff dipper's cancer," even though it is not the most common form of carcinoma resulting from this habit, and even though it has been reported from numerous anatomic sites other than the oral mucosa (larynx, ear canal, vagina, penis, bladder, rectum, soles of feet, dentigerous cyst).  It is, furthermore, now known that 16-51% of oral verrucous carcinomas are found in persons without tobacco habit.  Obviously, other etiologic agents may be involved, with immunosuppression, human papillomavirus and other viruses being most recently implicated.  Nevertheless, it cannot be denied that the most common site of occurrence for this cancer remains the oral mucosa and the majority of oral cases are found in persons who habitually chew tobacco or snuff.

The typical clinical presentation of oral verrucous carcinoma has long been known, as has its remarkably innocuous appearance and biological behavior when not associated with the devastating premalignancy, proliferative verrucous leukoplakia.  Relative frequency rates for biopsy service cases are also known: this cancer represents 1-10% of all oral squamous cell carcinomas diagnosed by U.S. hospitals and dental schools.10 In India, approximately 7% of oral cancers are verrucous carcinomas.

 The age-adjusted average annual incidence rate for oral verrucous carcinoma is 0.1-0.3/100,000 person-years (0.2-0.3 for males, 0.0-0.3 for females).  Among males over 64 years of age the incidence rate for verrucous carcinoma increases to 3.2/100,000 person-years.  Verrucous carcinoma is among the least common of the oral carcinomas, representing only 3% of the total.

Clinical Features


Pathology and Differential Diagnosis


Treatment and Prognosis


References (Chronologic Order)

Note: Click on underlined author's names for additional detail.

General references:

Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. Philadelphia, W. B. Saunders; 1995.

Elder D, Elenitsas R, Jaworsky C, Johnson B Jr. Lever's Histopathology of the skin, 8th edition. Philadelphia; Lippincott-Raven, 1997.

Sapp JP, Eversole LR, Wysocki GP. Contemporary oral and maxillofacial pathology. Mosby; St. Louis, 1997.

Odell EW, Morgan PR. Biopsy pathology of the oral tissues. London; Chapman & hall Medical, 1998.

Specific references:

1. Ewing J. Neoplastic diseases, 3rd edition. Philadelphia, W.B. Saunders, 1928.

2. Fridell HL, Rosenthal LN. The etiologic role of chewing tobacco in cancer of the mouth. Report of eight cases treated with radiation. J Am Med Assoc 1941; 116:2130-2135.

3. Ackerman LV. Verrucous carcinoma of the oral cavity. Surgery 1948; 23:670-678.

4. Fells A. Cancer of the mouth in southern India with an analysis of two hundred and nine operations. Brit Med J 1908;  1:1357-1358.

5. Bentall WG. Cancer in Travacore, South India. Brit Med J 1908; 2:1428-1431.

6. McCoy JM, Waldron CA. Verrucous carcinoma of the oral cavity: a review of forty-nine cases. Oral Surg Oral Med Oral Pathol 1981; 52:623-629.

7. Medina JE, Dichtel W, Luna MA. Verrucous-squamous carcinomas of the oral cavity: a clinicopathologic study of 104 cases. Arch Otolaryngol 1984; 110:437-440.

8. Tornes K, et al. Oral verrucous carcinoma. Int J Oral Surg 1985; 14:485-492.

9. Luna MA, Tortoledo ME. Verrucous carcinoma. In: Gnepp DR. ed. Pathology of the Head and Neck. London: Churchill Livingstone Inc, 1988:497-515.

10. Neville, BW, Damm DD, Allen CM et al. Oral and maxillofacial pathology. Philadelphia: W.B. Saunders; 1995:304-306.

11. Odell EW, Morgan R. Biopsy pathology of the oral tissues. London: Chapman & Hall Medical, 1998:229-233.

12. Kamath VV, et al. Oral verrucous carcinoma: an analysis of 37 cases. J Craniomaxillofac Surg 1989; 17:309-314.

13 Turner JE, Hodge SJ, Callen JP. Verrucous carcinoma in a renal transplant patient after long term immunosuppression. Arch Dermatol 1980; 116:1074-1076.

14. Fisker AV, Philipsen HP. Verrucous hyperplasia and verrucous carcinoma of the rat oral mucosa. Experimental carcinogenesis using 4-nitroguinoline 1-oxide. Acta Pathol Microbiol Immunol Scand 1984; 92A:437-445.

15. Eisenberg E, Rosenberg B, Krutchkoff DJ. Verrucous carcinoma: a possible viral pathogenesis. Oral Surg Oral Med Oral Pathol 1985; 59:52-57.

16 Shroyer KR, Greer RO, Frankhouser CA, et al. Detection of human papillomavirus DNA in oral verrucous carcinomas by polymerase chain reaction. Mod Pathol 1993; 6:669-672.

17. Kahn MA, Dockter ME, Hermann-Petrin JM. Proliferative verrucous leukoplakia. Four cases with flow cytometry analysis. Oral Surg Oral Med Oral Pathol 1994; 78:469-475.

18. Murrah VA, Batsakis JG. Proliferative verrucous leukoplakia and verrucous hyperplasia. Ann Otol Rhinol Laryngol 1994; 103:660-663.

19. Murti PR, Gupta PC, Bhonsle RB, et al. Smokeless tobacco use in India: effects on oral mucosa. In: Stotts RC, Schroeder KL, Burns DM (editors). Smokeless tobacco or health, an international perspective. Bethesda, Maryland: US Dept Health Human Services (NIH). NIH Publ No. 92-3461; 1992:51-65.

20. US Dept Health Human Services, PHS. The health consequences of using smokeless tobacco: a report of the advisory committee of the Surgeon General. Washington DC: NIH Publ No. 86-2874, 1986.

21. Connolly GN, Winn DM, Hecht SS, et al. The reemergence of smokeless tobacco. N Eng J Med 1986; 314(16):1020-1027.

22. US Dept HHS. Smokeless tobacco use in the United States, behavioral risk factor surveillance system, 1986. Morbid Mortal Wkly Rpt 1987; 36(22):337-340.

23. Glover ED, Glover PN. The smokeless tobacco problem: risk groups in North America. In: Stotts RC, Schroeder KL, Burns DM (editors). Smokeless tobacco or health, an international perspective. Bethesda, Maryland: US Dept Health Human Services (NIH). NIH Publ No. 92-3461; 1992: 3-10.

24. Bouquot JE, Kurland LT, Weiland LH. Primary salivary epithelial neoplasms in the Rochester, Minnesota population. J Dent Res 1979; 58:419. (abst)

25. Bouquot JE, Kurland LT, Weiland LH. Forty-five years of oral carcinoma in an United States population. J Oral Path 1985; 11:81.(abst)

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

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

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

29. Bouquot JE, Weiland LH, Kurland LT. Metastases to and from the upper aerodigestive tract in the population of Rochester, Minnesota, 1935-1984. Head Neck 1989; 11:212-218.

30. Bouquot JE, Weiland LH, Kurland LT. Multiple primary carcinomas of the upper aerodigestive tract (UAT); the complete experience of one U.S. community, 1935-1988. J Cancer Res Clin Oncol 1990; 116:358. (abst)

31. Bouquot JE, Weiland LH, Kurland LT. Laryngeal keratosis and carcinoma in the Rochester, Minnesota population, 1935-1984. Cancer Detect Prevent 1991; 15:83-91.

32. Bouquot JE, Gnepp DR. Laryngeal precancer--a review of the literature, commentary and comparison with oral leukoplakia. Head Neck 1991; 13: 488-497.

33. Bouquot JE, Kurland LT. Weiland LH. Incidence of oral verrucous carcinoma in a U.S. community with minimal smokeless tobacco consumption. J Oral Pathol Med 1996; 25:271.

34. Centers for Disease Control. State tobacco control highlights--1996. CDC Publ No 099-4895. CDC, Atlanta, Georgia, 1996.

35. Practice Management Information Corporation. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), 4th edition. Los Angeles, California; Practice Management Information Corp, 1993.

36. Kleinbaum DG, Kupper LL, Morganstern H. Epidemiologic research: principles and quantitative methods. Belmont, California, Lifetime Learning Publications, 1982.

37. Slemp C, Keener B, German RR. Cancer in West Virginia 1993-1995. Charleston, West Virginia: Bureau for Public Health (Office of Epidemiology and Health Promotion), 1997.

38. West Virginia Division of Public Health. Tobacco use and its health consequences, a report on the leading cause of death and disability in West Virginia. Charleston, West Virginia: WV Dept Health Human Resources, 1990.

39. Slemp C, Keener B, German RR. Cancer in West Virginia 1993. Charleston, West Virginia; Bureau for Public Health (Office of Epidemiology and Health Promotion), 1995.

40. Slemp C, Keener B, German RR. Cancer in West Virginia 1993-1994. Charleston, West Virginia: Bureau for Public Health (Office of Epidemiology and Health Promotion), 1996.

41. Horm JW, Asire AJ, Young JL Jr, et al. SEER Program: cancer incidence and mortality in the United States, 1973-81. NIH Publ No. 85-1837. Bethesda, Maryland; NCI, 1985.

42. Kleinman DV, Crossett LS, Gloeckler Ries LA, et al. Cancer of the oral cavity and pharynx: a statistics review monograph 1973-1987. Bethesda, Maryland; DHHS Publ. No. PHS91-50212, 1991.

43. Reis LAG, Kosary CL, Hankey BF, et al (eds). SEER cancer statistics review: 1973-1994: tables and graphs. Bethesda, Maryland: Nat Cancer Inst. NIH Pub No. 97-2789, 1997.

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

45. Winn DM. Smokeless tobacco and cancer: the epidemiologic evidence. CA1988; 38:236-243.

46. Rodu B. An alternative approach in smoking control. Am J Med Sci 1994; 308:32-34.

47. Vigneswaran N, Rodu B, Cole P. Tobacco use and cancer, a reappraisal. Oral Surg Oral Med Oral Pathol 1995; 80:178-182.


Table 1: Histopathologic types of upper aerodigestive tract (UAT) carcinomas diagnosed in Rochester, Minnesota residents, 1935-1984, ranked by frequency of intraoral lesions. Lesions of the major salivary glands and nasal/paranasal sinuses are excluded.


Number of Lesions



Squamous cell carcinoma 65 50 46 49 210
Carcinoma in situ 15 8 5 7 35
Microinvasive squamous cell carcinoma 7 6 3 3 19
Metastatic carcinoma to the UAT 0 4 2 0 6
Adenocarcinoma (minor glands) 1 2 4 0 7
Verrucous carcinoma 0 2 0 0 2
Lymphoepithelioma 0 1 7 0 8
Basal cell carcinoma 10 0 0 0 10
       Total * 98 73 67 59 297

        * no primary cases were found of malignant melanoma, spindle cell carcinoma, basaloid squamous carcinoma, or                         adenosquamous carcinoma

Table 2: Average annual incidence rates for primary invasive carcinomas of the upper aerodigestive tract in the Rochester, Minnesota population, 1935-1984, age-adjusted to the 1970 U.S. white population. Totals in right-hand column are also gender adjusted to 1970 U.S. white population.

Anatomic Site

# Cases/100,000 person-years *
Males Females Total
Lip vermilion 8.2 (74)** 0.8 (9) ** 4.1 (83)**
Intraoral mucosa 5.4 (38) 2.1 (23) 3.6 (61)
Verrucous carcinoma 0.2 (2) 0.0 (0) 0.1 (2)
Pharyngeal mucosa 5.2 (38) 2.0 (22) 3.4 (60)
Laryngeal mucosa 7.0 (49) 0.3 (3) 3.3 (52)
Nasal/Paranasal sinuses 0.7 (6) 0.6 (6) 0.7 (12)
Major salivary glands 1.1 (11) 1.3 (13) 1.3 (24)
All primary carcinomas 30.0 (216) 7.2 (76) 17.3 (292)

 * population base: 900,312 person-years for males, 1,102,916 person-years for females
** numbers in parentheses represent actual number of cases, not incidence rates; carcinomas in situ and metastases
    to the upper aerodigestive tract are excluded from the above data



Note: To see enlarged photo, click on the left-hand picture; 
return here with your BACK ARROW button.