Physicians Turn to HPV Testing In Women With AGUS Pap Results


VANCOUVER, CANADA — When Kaiser Permanente instituted testing for human papillomavirus in 2001, physicians were instructed not to test for the virus as a way to triage patients with Pap results showing atypical glandular cells of undetermined significance.

Clinicians “paid no attention whatsoever” to this guideline, however, resulting in data on 877 women with atypical glandular cells of undetermined significance (AGUS) smears who underwent testing for the human papillomavirus (HPV) and biopsies, Walter Kinney, M.D., said at the 22nd International Papillomavirus Conference.

National guidelines recommend HPV testing in two situations: to help manage women with Pap smears showing atypical squamous cells of undetermined significance (ASCUS), or as cotesting with Pap smears for cervical screening in women older than 30 years.

HPV tests were positive in 33% of the women with AGUS. Of these, 33% had cervical intraepithelial neoplasia grades 2/3 or higher (CIN 2/3+). Among HPV-negative women, 3% had CIN 2/3+, said Dr. Kinney of the Permanente Medical Group, Sacramento.

Of more interest to investigators were the women whose initial colposcopies produced negative biopsy results. Their HPV status at the time of AGUS diagnosis was more predictive than biopsy results of the likelihood of developing cervical abnormalities during a 12-month follow-up, he said at the conference, sponsored by the University of California, San Francisco.

Among 95 women who were initially HPV positive but had negative biopsies, 24 (25%) developed CIN 2/3+ during follow-up. None of 260 women who were HPV negative with benign biopsies at their initial evaluation developed CIN 2/3+.

The lead investigator in this study was Barbara Fetterman, Ph.D., of the Permanente Medical Group, Oakland, Calif. In a poster presentation at the meeting, she said the “current American Society for Colposcopy and Cervical Pathology recommendations for rescreening [at 4–6 month intervals for four times] in women with atypical glandular cell cytology, and a negative initial evaluation could be replaced with a single rescreen in 12 months if a woman is also HPV negative.”

Kaiser clinicians also crossed the HPV guidelines to test for HPV in 161 women with Pap results showing “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions” (ASC-H).

Results showed that HPV positivity fell significantly after age 30, from a rate of 90% in women younger than 30, to 69% of women aged 30–39 years, 45% of women aged 40–49 years, and 30% of women aged 50 and older, Dr. Fetterman reported in a separate poster.

Among 125 of the women with ASC-H who also had biopsies, 38% had CIN2/3+, including one adenocarcinoma in situ. All women with CIN2/3+ were HPV positive. As time goes on, there probably will be an HPV-negative woman with ASC-H who has CIN2–3+, Dr. Kinney acknowledged, but the correlation between a negative HPV test and low risk for CIN 2/3+ in women with ASC-H is useful.

Dr. Fetterman described how the high negative predictive value of the HPV test for CIN 2/3+ and the falling HPV positivity rate with age make it useful to triage women with ASC-H. HPV triage of women with ASC-H would send 64% of women of all ages and 48% of women aged 30 and over to colposcopy. These rates are similar to the 56% of women with ASC US sent to colposcopy in the National Cancer Institute's ALTS study (ASCUS/Low-Grade Squamous Intraepithelial Lesions Triage Study), suggesting that “HPV triage of ASC-H may be useful in clinical practice, particularly in women age 30 and over,” she said.

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