Carcinoma In situ of the Cervix and its TreatmentRecurrencee

Frederick R. Jelovsek MD

"I was recently diagnosed with carcinoma in situ or severe dysplasia of the cervix, I had a LEEP procedure and recently had a normal pap test. I was wondering if I am at increased risk for this to happen again and if it comes back does it start as minor and progress to severe?"

"I am 29 years old with 2 children and not on any medication. " anonymous

The classifications of cervical dysplasia are sometimes confusing. Pap smears, which are a screening tool and not the "gold standard", are graded from atypical cells of undetermined significance (ASCUS), through low grade squamous intraepithelial lesions (LGSIL) to high grade squamous intraepithelial lesions (HGSIL). The actual biopsies are classified as mild, moderate and severe cervical dysplasia or cervical intraepithelial neoplasia (CIN). Usually LGSIL on a Pap smear corresponds to mild dysplasia and HGSIL is correlated to either moderate or severe dysplasia on biopsy. To make things even more confusing, severe dysplasia may also be called carcinoma in situ of the cervix.

All of these epithelial (cervical skin) changes simply refer to what percent of the epithelium has cells in it that have increased nuclear activity. If you look at the image below, you will see normal cells the full thickness of the skin on the left and abnormal cells the full thickness of skin on the right. Thus this particular tissue section shows the full range of cell changes from normal, to mild dysplasia, to moderate dysplasia, to severe dysplasia/carcinoma in situ. Click to see image

If 100% of the thickness has abnormal cells on biopsy, that is classified as carcinoma in situ. If the top third of the epithelium is abnormal, that is classified as severe dysplasia. In truth, pathologists cannot always differentiate between about 70% and 100% of the thickness so that severe dysplasia and carcinoma in situ are often lumped together to bring attention to the seriousness of the lesion. Mild dysplasia would be changes confined to the lower one-third of the epithelial thickness and moderate dysplasia refers to changes that extend from the base up into the middle two-thirds of the thickness.

LEEP procedure is now the most common method of treating moderate and severe dysplasia of the cervix because it can usually be done in the office. It uses a wire through which electricity is passed so that dysplasia tissue can be cut off of the surface of the cervix.

In one study that looked a recurrence of dysplasia after LEEP, 72.5% of the patients were cured while 27.5% had a recurrence (1). Of the women who had recurrence, about 66% were still high grade lesions of severe dysplasia/carcinoma in situ. The remainder were lower grade lesions. Recurrence was higher if there was dysplasia at the cut margins of the specimen or if the changes went down deep into the endocervical glands. Therefore if the specimen showed no dysplasia at the margins, LEEP was 85% curative while if margins were positive, the LEEP was only 60% curative. If margins were negative and there was no endocervical involvement, LEEP was 91% curative versus 80% if glands were involved.

Almost any method of treatment that destroys abnormal dysplastic cells has been used to cure cervical dysplasia. These include cryotherapy (freezing), laser excision and ablation, LEEP, conization (cutting out the tissue with a knife) and heat or diathermy. Knife conization and LEEP are the most commonly used for severe dysplasia.

One small study found a slightly better cure rate for cold knife conization (90%) than for LEEP (79%) (2). However there was much more difficulty in following up after the procedure with adequate colposcopy if the knife conization was performed (39% adequate visualization) versus LEEP (71% adequate visualization).

To determine this, we have to go back to some older studies in which women with the disease were not treated at all, but just followed. Rates of progression of carcinoma in situ of the cervix to frankly invasive cancer range from about 22% to 60% when followed more than 10 years (3, 4). In other words about half of the time, these cervical changes do not progress to cancer, the other half they do.

Hysterectomy is slightly more effective than cervical conization to cure severe cervical dysplasia but it is not 100%. After the cervix is removed, dysplasia changes can take place at the end of the vagina where the cervix used to be (5, 6, 7) but the incidence of invasive cancer of the vagina after hysterectomy is only about 1% if NO follow up Paps take place.

Most investigators believe that HPV, human papilloma virus, subtypes 16 and 18 are primary cause of most cases of cervical cancer. Scientists are working to develop vaccines against these viruses in hopes that immunization of women at a very young age will prevent infection (8). A company called Medimmune has a vaccine in testing but keep in mind it will still be many years before it has been adequately tested.