Cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix.^[1] 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.^[2] 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 & 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 the changes early, while it has not yet progressed to invasive carcinoma, and is easier to cure. An abnormal Pap smear 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 to the next grade, or regress.^[1]

CIN is classified in grades:

• CIN1 (Grade I), the least risky type, represents only mild dysplasia, or abnormal cell growth^[2]. This corresponds to a low grade squamous intraepithelial lesion (LGSIL or LSIL) result on a Pap test.^[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.
• CIN2/3 correspond to high grade squamous intraepithelial lesions (HSIL).^[3] Sometimes this is further divided:
  • CIN2 (Grade II): Moderate dysplasia confined to the basal 2/3 of the epithelium
  • CIN3 (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.

Normal cervical epithelium (H&E stain).

Grade I CIN.

Grade II CIN.

Grade III CIN.

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] If caught early, CIN is usually curable.^[4]

Risk Factors

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

• Women who have had multiple sexual partners
• Women who become infected by a higher risk types of HPV, such as 16, 18, 31 or 45.
• Women who smoke
• Women who are immunodeficient

Progression

Cases of CIN are thought by some to progress through these stages toward cancer in a linear fashion.^[2][5][6]

However most CIN spontaneously regress. 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] [2][7]}

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

In many cases, CIN will regress without treatment. A diet rich in fruits and vegetables, smoking avoidance and condom use^[8] increases regression of cervical dysplasia.

CIN is curable, although the lifetime recurrence rate is 20%. Methods used to treat CIN require removal or destruction of the surface cells of the cervix. These methods include cryocautery, electrocautery, laser cautery, LEEP, and cervical conization. Therapeutic vaccines are also in development.

See also

• Dyskaryosis

References