ASCUS PAPS and HPV

Pap smears have significantly decreased the incidence of cervical cancer in the United States. Pap smears detect changes in cervical cells that increase the risk of developing a cervical cancer, sometimes called precancerous cells. However the Pap test is not perfect. It does not detect all precancerous abnormalities. It also is sometimes equivocal…showing changes that are slightly abnormal but not abnormal enough to be called precancerous. These changes are called "atypical squamous cells of uncertain significance" or ASCUS.

ASCUS accounts for about 5-10% of all Pap smear results. The best management of ASCUS paps has confused patients and physicians alike since its description in the Bethesda guidelines These are guidelines initially developed in 1991 by a large group of experts relating to the evaluation, reporting and management of pap smears, the conference meets in Bethesda Maryland, hence the name. The majority of ASCUS paps will ultimately be nothing to worry about but approximately10% will be found to harbor a precancerous lesion. The Bethesda guidelines for reporting and ultimately managing abnormal pap smears were revised in 2001. The revision reflects our changing knowledge about the causes and development of cervical cancers and advances in medical testing.

The cause of precancerous changes and cancer of the cervix is a virus called the human papillomavirus (HPV). This is a sexually transmitted virus. It is found in about 40% of young sexually active women and in a smaller percent of women over the age of 30. There are about 100 types of HPV only a few of which have been linked to cervical cancer. These are called high-risk types. The presence of HPV is generally transitory, the majority of infections are gone after a year or so, but some will persist for decades. Only a very small percentage of women with HPV will ultimately develop cervical cancer and that number is even less if precancerous changes are detected and treated appropriately. Potentially precancerous changes used to be called mild, moderate and severe dysplasia or CIN 1, CIN 2 and CIN 3. Newer terminology classifies the changes into either a low grade or high-grade lesion. This reflects newer data that shows that the majority of low-grade lesions are transient, reflecting infection with HPV, whereas the high-grade lesions, also caused by HPV, are more likely to persist and develop into a cancer if left untreated.

Management of pap smears showing high-grade or low-grade lesions is relatively straightforward. Women undergo a colposcopy. This involves examining the cervix with the colposcope, which I refer to as binoculars on wheels. This allows magnification of the cervix and after application of vinegar to the cervix the ability to see abnormal areas. These areas are then biopsied and sent to the pathologist for evaluation. Follow-up and treatment is based on these results.

Management of the ASCUS paps is more controversial. Traditionally these can be managed by either immediate colposcopy or follow-up paps. The 2001 Bethesda guidelines endorsed a third option. With the understanding that the presence of HPV is necessary for the development of cervical cancer and the availability and sensitivity of a DNA test for HPV, this test can be used to decide how to manage ASCUS paps. Women who have an ASCUS pap and test negative for high-risk HPV can be reassured that they do not have a significant lesion whereas those with positive HPV tests should be referred for colposcopy. Between 30-60% of women with ASCUS paps will test positive for high-risk HPV depending on the age of the woman; the incidence decreases with age.

Articles have appeared in both the medical and popular literature exploring the use of only HPV testing as an initial screen for abnormal cervical changes done instead of or in conjunction with the traditional pap. Dubbed the DNA pap the idea is that if the test were negative then yearly pap tests would not be necessary. The HPV test, while useful in the management of ASCUS paps, has not been approved for initial screening either by the FDA or expert medical groups such as the one that devised the Bethesda guidelines.

The 2001 Bethesda guidelines will simplify and hopefully make more consistent the management of ASCUS and other abnormal paps. However the guidelines are not intended to replace the clinical judgment of your gynecologist. Future and ongoing research studies will explore the usefulness of HPV testing in initial screening for cervical abnormalities. A vaccine for HPV is currently in clinical trials and if effective will hopefully mark the end of all cervical cancers, the ultimate goal of any screening and treatment program for HPV and the resultant precancerous changes of the cervix.