Natural History, Incidence, and Mortality

Natural History, Incidence, and Mortality

In the United States in 2008, it is estimated that 11,070 cases of invasive cervical cancer will be diagnosed and that 3,870 women will die of the disease.[1] These rates have been improving steadily, with a 70% drop between 1950 and 1970 and a 40% drop between 1970 and 1999.[2] This improvement has been attributed largely to screening with the Papanicolaou test.

Invasive squamous carcinoma of the cervix results from the progression of preinvasive precursor lesions called cervical intraepithelial neoplasia (CIN), or dysplasia. CIN is histologically graded into mild dysplasia (CIN 1), moderate dysplasia (CIN 2), or severe dysplasia (CIN 3). Not all of these lesions progress to invasive cancer; many mild and moderate lesions regress. A further categorization, the Bethesda system, is based on cytologic findings: Atypical squamous cells of undetermined significance (ASCUS) or cannot rule out low-grade squamous intraepithelial lesions (LSIL), LSIL (consisting of cytologic atypia and CIN 1), and high-grade squamous intraepithelial lesions (HSIL), primarily CIN 2–3 plus carcinoma in situ.[3]

The rate at which invasive cancer develops from CIN is usually slow, measured in years and perhaps decades.[4] This long natural history provides the opportunity for screening to effectively detect this process during the preinvasive phase, thus allowing early treatment and cure. Because many of these preinvasive lesions (especially LSIL) would have never progressed to invasive cancer,[5-7] screening also runs the risk of leading to treatment of women who do not need to be treated.

The leading etiologic factor in the development of preinvasive and invasive cervical cancer is infection with specific types of human papillomavirus (HPV), which is transmitted by sexual contact. Thus, sexually inactive women rarely develop cervical cancer, while sexual activity at an early age with multiple sexual partners is a strong risk factor. About 95% of women with invasive cervical cancer have evidence of HPV infection.[8-11] Many women with HPV infection, however, never develop cervical cancer; thus this infection is necessary but not sufficient for development of cancer.[12]

Although cervical cancer mortality increases with age (maximum mortality for white women is between the ages of 45 years and 70 years; for black women it is in their 70s),[2] the prevalence of CIN is highest among women in their 20s and 30s. Mortality is rare among women younger than 30 years; HSIL is rare among women older than 65 years who have been previously screened. About 70% of ASCUS and CIN 1 lesions regress within 6 years, while about 6% of CIN 1 lesions progress to CIN 3 or worse. About 10% to 20% of women with CIN 3 lesions progress to invasive cancer.[4,7,13]

Cervical cancer mortality is about 40% higher in black women younger than 65 years than in white women of the same age. Among women older than 65 years, cervical cancer mortality for black women is more than 250% higher than for white women.[2] In either case, mortality is rare among women of any age who have regular screening.

References

1. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008. 
   
   
2. Ries LA, Eisner MP, Kosary CL, et al.: SEER Cancer Statistics Review, 1973-1999. Bethesda, Md: National Cancer Institute, 2002. Also available online. Last accessed February 12, 2009. 
   
   
3. Solomon D, Davey D, Kurman R, et al.: The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 287 (16): 2114-9, 2002.  [PUBMED Abstract]
   
   
4. Holowaty P, Miller AB, Rohan T, et al.: Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 91 (3): 252-8, 1999.  [PUBMED Abstract]
   
   
5. Nasiell K, Roger V, Nasiell M: Behavior of mild cervical dysplasia during long-term follow-up. Obstet Gynecol 67 (5): 665-9, 1986.  [PUBMED Abstract]
   
   
6. Nash JD, Burke TW, Hoskins WJ: Biologic course of cervical human papillomavirus infection. Obstet Gynecol 69 (2): 160-2, 1987.  [PUBMED Abstract]
   
   
7. Melnikow J, Nuovo J, Willan AR, et al.: Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol 92 (4 Pt 2): 727-35, 1998.  [PUBMED Abstract]
   
   
8. Bosch FX, Manos MM, Muñoz N, et al.: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87 (11): 796-802, 1995.  [PUBMED Abstract]
   
   
9. Wallin KL, Wiklund F, Angström T, et al.: Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med 341 (22): 1633-8, 1999.  [PUBMED Abstract]
   
   
10. Alani RM, Münger K: Human papillomaviruses and associated malignancies. J Clin Oncol 16 (1): 330-7, 1998.  [PUBMED Abstract]
    
    
11. Walboomers JM, Jacobs MV, Manos MM, et al.: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189 (1): 12-9, 1999.  [PUBMED Abstract]
    
    
12. Ho GY, Bierman R, Beardsley L, et al.: Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338 (7): 423-8, 1998.  [PUBMED Abstract]
    
    
13. Arends MJ, Buckley CH, Wells M: Aetiology, pathogenesis, and pathology of cervical neoplasia. J Clin Pathol 51 (2): 96-103, 1998.  [PUBMED Abstract]
    
    

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