Natural Progression of an Abnormal Pap

Frederick R. Jelovsek MD

Approximately 2-5% of Pap smears will have an abnormal result. The usual abnormal result categories are:

ASCUS - Atypical cells of uncertain significance
low grade squamous intraepithelial neoplasia (LGSIL) or mild dysplasia
high grade squamous intraepithelial neoplasia (HGSIL) consistent with moderate or severe dysplasia

Many women want to know how serious these findings are. The way we know what the natural progression of these abnormal Paps is to follow the woman without treating or doing anything to alter the normal progression (worsening) or regression (improvement) of these Paps.

A recent study, Melnikow J: Natural history of cervical squamous intraepithelial lesions: A meta-analysis. Obstet Gynecol 1998;92:727-35, looked at all scientific studies in the literature since 1970 in which women with abnormal Paps were followed but not treated. They then analyzed how often the specific Pap smear improved on it's own and how often it progressed to a worse lesion:

Abnormal Pap Smear
Natural Progression and Regression

Abnormal Class	Regression to Normal	Progression to higher grade over 24 Months	Progression to invasive cancer over 24 Months
ASCUS	68%	7%	0.25%
LGSIL	47%	21%	0.15%
HGSIL	35%	23%	1.44%

The studies analyzed took the Pap smear on entry as the true finding when in fact we know the Pap is a screening test and as such has some false negatives (could explain progression) and false positives (could explain regression).

How does HPV (human papilloma virus) affect progression of the Pap? In one study(1), The rate of CIN progression was higher with HPV (50.5%) than without HPV (35.4%). Of the CIN cases with HPV 16, 56.5% progressed, while 30.8% of the CIN cases with HPV 6 and/or 11 and 35.4% of the CIN cases without HPV progressed. In other words, HPV subtype 16 was associated with a higher progression rate but not all subtypes of HPV.

Another older study before HPV sub typing(2), looked at progression or regression of a Pap smear showing HPV.