Cervical Intraepithelial Neoplasia

Cervical Intraepithelial Neoplasia (CIN) or cervical dysplasia is the term used to describe a pathological disease state of the uterine cervix (the lower part of the cervix extending to the vagina) caused by infection from the Human Papilloma virus (HPV). This condition has been found to precede the development of cervical cancer. Identification of CIN, which is a precancerous state, by pap smear screening, offers the opportunity to treat and remove the diseased tissue from the cervix to prevent development of cervical cancer.

About 250,000 to 1 million women are diagnosed with CIN every year and is most commonly identified in women between the ages of 25 and 35.

Progression to cancer from the time of HPV infection can range from 3 to 40 years with an average of 15 years. So there is generally adequate time to identify and treat the precancerous condition.

Classification of CIN

There are three grades of CIN based on the severity of epithelial changes viewed on pap smear. The grades roughly correspond to the probability of progression to cancer.

• CIN 1: this is also classified as Low-grade squamous intraepithelial lesion (LSIL) and is marked by mild dysplasia. There is low risk of progression to cancer. Nearly 90% regress to normal even if left untreated after 2 years. 1% progresses to invasive cancer
• CIN 2 and 3 are both classified as High-grade squamous intraepithelial lesion (HSIL) and have moderate to severe dysplasia with higher rates of progression to cancer
  • CIN 2: about 50% may regress completely and 5% progress to invasive cancer when left untreated.
  • CIN 3: This is severe dysplasia with deeper involvement of the skin on the cervix. This may also be labelled as carcinoma in situ (CIS) which refers to cancer that has not spread beyond it’s initial site. 12% of CIN 3 progress to invasive cancer.

Causes and risk factors for CIN

• Infection with HPV: There are several types of HPV. Infection with the high risk types as associated with CIN and Cervical Cancer. Types 16,18, 31 and 33 are the most commonly implicated
• Poor immunity: This can be from diseases leading to immunodeficiency like several inherited conditions of from HIV infection and AIDS. Low immunity allows rapid replication of the HPV virus and quicker progression to late CIN stages and cancer
• Poor diet
• Multiple sexual partners
• Early onset of sexual activity
• Lack of barrier contraception
• Smoking

Screening and diagnosis of CIN

CIN is asymptomatic, meaning women face no discomfort and have no complaints. The only way of identifying the presence of CIN is by doing screening pap smears, followed by colposcopy and biopsy

• Pap Smear: this is a simple procedure which can be done in an outpatient setting by your primary care physician. The woman is asked to lie down with legs propped up. Using a device to visualize the cervix, a thin flat stick similar to an ice cream stick and a brush are rotated through the cervix to collect cells. These cells are then spread onto a slide and studied under a microscope. Abnormal cells are reported with recommendation for further testing
• Colposcopy: This involves using a magnifying scope to examine the surface of the cervix. It allows to detect areas of abnormal tissue and to easily obtain tissue for biopsy. Procedures to remove abnormal tissue may also be carried out under colposcopy.
• Biopsy: This is done to definitively identify the presence of CIN or cancer in the collected tissue.
• HPV DNA testing: this is done using the same cells obtained during a pap smear. Testing for DNA increases the accuracy of identifying HPV infection.

Screening using pap smear is recommended for all women from the age of 21 regardless of age of onset of sexual activity and vaccination

Treatment of CIN

The treatment options vary by the grade of CIN. For grade 1 CIN, as the risk of progression to cancer is low, repeated testing with frequent pap smears may be the only recommended step. For CIN 2 and 3 and also for CIS, ablation and resection of the abnormal tissue is recommended. Various methods are available.

• Ablation using cautery: The abnormal tissue is destroyed completely using laser, electricity current or cryotherapy.
• Loop Electrical Excision Procedure (LEEP): this is a resection procedure where the abnormal area of tissue is cut out using an electrified wire. The tissue can then be examined to confirm complete removal.
• Cold knife cone biopsy (conization): A cone shaped area of tissue is removed from around the cervical opening. This also provides tissue for biopsy. Conization is preferred for more severe forms of CIN.
• Hysterectomy: This is a surgical procedure to remove the entire uterus along with the cervix. This is done in very severe CIN and CIS which are not responsive to other forms of therapy. This may also be recommended in older women who have completed their family and have other comorbid conditions like excess uterine bleeding.

All the resection procedures carry the side effect of cervical scarring with narrowing of the opening with cervical stenosis. Conization carries a worse risk than LEEP.

Prevention of CIN

A vaccination is now available for protecting against infection from HPV. This is composed of 4 HPV types, 16, 18, 31 and 33 and is recommended to be administered in all girls and young women from age 9 to 26 years. It is also recommended for boys and young men from 9 to 26 years. Pap smear screening ought to be continued regardless of vaccination status.

References

1. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62(3):147-72
2. Feldman S, et al. Screening for cervical cancer. Accessed April 30, 2019.
3. Genital HPV infection: Fact sheet. Centers for Disease Control and Prevention. Accessed April 30, 2019.