Cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia
Classification and external resources
ICD-10	D06, N87
ICD-9	233.1, 622.10
MeSH	D018290

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix.^[1] CIN is not cancer, and is usually curable.^[2] Most cases of CIN remain stable, or are eliminated by the host's immune system without intervention. However a small percentage of cases progress to become cervical cancer, usually cervical squamous cell carcinoma (SCC), if left untreated.^[3] The major cause of CIN is chronic infection of the cervix with the sexually transmitted human papillomavirus (HPV), especially the high-risk HPV types 16 or 18. Over 100 types of HPV have been identified. About a dozen of these types appear to cause cervical dysplasia and may lead to the development of cervical cancer. Other types cause warts.

The earliest microscopic change corresponding to CIN is dysplasia of the epithelial or surface lining of the cervix, which is essentially undetectable by the woman. Cellular changes associated with HPV infection, such as koilocytes, are also commonly seen in CIN. CIN is usually discovered by a screening test, the Papanicolaou or "Pap" smear. The purpose of this test is to detect potentially precancerous changes. Pap smear results may be reported using the Bethesda System. An abnormal Pap smear result may lead to a recommendation for colposcopy of the cervix, during which the cervix is examined under magnification. A biopsy is taken of any abnormal appearing areas. Cervical dysplasia can be diagnosed by biopsy.

Grades

Depending on several factors such as the type of HPV and the location of the infection, CIN can start in any of the three stage, and can either progress, or regress.^[1]

CIN is classified in grades:

Histology Grade	Corresponding Cytology	Description	Image
–	–	Normal cervical epithelium
CIN 1 (Grade I)	LSIL[4]	The least risky type, represents only mild dysplasia, or abnormal cell growth.[3] It is confined to the basal 1/3 of the epithelium. This corresponds to infection with HPV, and typically will be cleared by immune response in a year or so, though can take several years to clear.
CIN 2/3	HSIL	Formerly subdivided into CIN2 and CIN3.
CIN 2 (Grade II)		Moderate dysplasia confined to the basal 2/3 of the epithelium
CIN 3 (Grade III)		Severe dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. This lesion may sometimes also be referred to as cervical carcinoma in situ.

Incidence

Between 250,000 and 1 million American women are diagnosed with CIN annually. Women can develop CIN at any age, however, women generally develop it between the ages of 25 to 35.^[1]

Risk factors

Some risk factors that have been found to be important in developing CIN are:^[1]

• Women who become infected by a "high risk" types of HPV, such as 16, 18, 31, or 45
• Women who have had multiple sexual partners
• Women who smoke
• Women who are immunodeficient
• Women who give birth before age 17

Progression and regression

It used to be thought that cases of CIN progressed through these stages toward cancer in a linear fashion.^[3][5][6]

However most CIN spontaneously regress. Left untreated, about 70% of CIN-1 will regress within two years, and 90% within two years.^{[clarification needed][7]} About 50% of CIN 2 will regress within 2 years without treatment. Progression to cancer typically takes 15 (3 to 40) years. Also, evidence suggests that cancer can occur without first detectably progressing through these stages and that a high grade intraepithelial neoplasia can occur without first existing as a lower grade.^[1][3][8]

It is thought that the higher risk HPV infections, have the ability to inactivate tumor suppressor genes such as the p53 gene and the RB gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.^[1]

Treatment

Treatment for higher grade CIN involves removal or destruction of the neoplastic cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization. Therapeutic vaccines are also in development. The lifetime recurrence rate of CIN is about 20%,^{[citation needed]} but it isn't clear what proportion of these cases are new infections rather than recurrences of the original infection.

A number of risk factors have been shown to increase a woman's likelihood of developing CIN,^[9] including poor diet, poor personal hygiene, multiple sexual partners, lack of condom use, and cigarette smoking. Using condoms increases regression of cervical dysplasia.^[10]

See also

• Dyskaryosis

References

1. ^ ^{a b c d e f} Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 718–721. ISBN 978-1-4160-2973-1. 
2. ^ Cervical Dysplasia: Overview, Risk Factors
3. ^ ^{a b c d} Agorastos T, Miliaras D, Lambropoulos A, Chrisafi S, Kotsis A, Manthos A, Bontis J (2005). "Detection and typing of human papillomavirus DNA in uterine cervices with coexistent grade I and grade III intraepithelial neoplasia: biologic progression or independent lesions?". Eur J Obstet Gynecol Reprod Biol 121 (1): 99–103. doi:10.1016/j.ejogrb.2004.11.024. PMID 15949888. 
4. ^ Park J, Sun D, Genest D, Trivijitsilp P, Suh I, Crum C (1998). "Coexistence of low and high grade squamous intraepithelial lesions of the cervix: morphologic progression or multiple papillomaviruses?". Gynecol Oncol 70 (3): 386–91. doi:10.1006/gyno.1998.5100. PMID 9790792. 
5. ^ Hillemanns P, Wang X, Staehle S, Michels W, Dannecker C (2006). "Evaluation of different treatment modalities for vulvar intraepithelial neoplasia (VIN): CO(2) laser vaporization, photodynamic therapy, excision and vulvectomy". Gynecol Oncol 100 (2): 271–5. doi:10.1016/j.ygyno.2005.08.012. PMID 16169064. 
6. ^ Rapp L, Chen J (1998). "The papillomavirus E6 proteins". Biochim Biophys Acta 1378 (1): F1–19. PMID 9739758. 
7. ^ Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de Sanjose S, Bruni L, Tortolero-Luna G, Kjaer SK, Muñoz N (August 2008). "Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia". Vaccine 26 (Supplement 10): K1–16. doi:10.1016/j.vaccine.2008.05.064. PMID 18847553. 18847553. 
8. ^ Monnier-Benoit S, Dalstein V, Riethmuller D, Lalaoui N, Mougin C, Prétet J (2006). "Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions". J Clin Virol 35 (3): 270–7. doi:10.1016/j.jcv.2005.09.001. PMID 16214397. 
9. ^ Murthy NS, Mathew A. (February 2000). "Risk factors for pre-cancerous lesions of the cervix". European Journal of Cancer Prevention 9 (1): 5–14. doi:10.1097/00008469-200002000-00002. PMID 10777005. 10777005. 
10. ^ Hogewoning CJ, Bleeker MC, van den Brule AJ, Voorhorst FJ, Snijders PJ, Berkhof J, Westenend PJ, Meijer CJ. (2003-12-10). "Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial.". Int J Cancer 107 (5): 811–6. doi:10.1002/ijc.11474. PMID 14566832.