Cervical intraepithelial neoplasia

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:

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.^[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%, 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