Karen LuskyBased on the premise that simpler is better, the
2006 American Society for Colposcopy and Cervical Pathology (ASCCP) consensus
guidelines in many ways streamline the management of women with abnormal
cervical cytology and histology. Revisions to the existing 2001 guidelines
aren’t dramatic, sources say, but expect HPV DNA testing to have a stronger
evidence-based role in the revamped version.
About 100 delegates from 28 national professional organizations, including the CAP, and federal health care agencies voted on decision points for the guidelines at a consensus conference the ASCCP hosted in September at the National Cancer Institute. The ASCCP expects the guidelines to be published next spring.
The impetus for revising the ASCCP guidelines is to keep pace with an "exploding field" in terms of clinical trials in progress "and an increased understanding of the biology" of cervical cancer, says David C. Wilbur, MD, who is chair of the CAP Cytopathology Committee and served as one of three CAP voting delegates at the consensus conference. He is director of cytology at Massachusetts General Hospital, Boston.
"Simplification of the guidelines is a theme," says Mark Spitzer, MD, ASCCP president and chairman of the Department of Obstetrics and Gynecology at Brookdale University Hospital and Medical Center, Brooklyn, NY. He characterizes the 2001 guidelines as "complex and sometimes difficult for clinicians to follow who don’t spend their entire life doing this stuff."
As one example of the aim to simplify, the guidelines "merge the management" of women with low-grade SIL (squamous intraepithelial lesion) Pap smears and those with carcinogenic HPV-positive ASC-US (atypical squamous cells of undetermined significance) Pap smears, says Dr. Spitzer. The "evidence seemed to point to the fact" that women with these abnormal cytologies have the "same risk of high-grade disease and are basically indistinguishable in their clinical outcomes," he says.
The guidelines will also standardize time frames for the followup of abnormal cytology. The 2001 guidelines’ followup protocols vary: Some are four to six months, while others are six to 12 months or 12 months only. So "we tried to find a uniform approach where most cytological followup is six to 12 months—and 12 months for HPV followup," Dr. Spitzer says.
He notes that the data supporting HPV testing is "stronger" than it was in 2001. "Where we had a lot of preliminary data [then], we now have published data," he says.
New recommendations will help clinicians grapple with the question: "If a woman [30 years or older] has normal cytology [on a Pap smear] but is positive for carcinogenic HPV, then what do you do?" says Edward J. Wilkinson, MD, who chaired the HPV DNA Testing Guidelines Committee and is professor and vice chairman of the Department of Pathology, University of Florida College of Medicine, Gainesville.
The 2001 guidelines don’t address that because they were developed before American Cancer Society guidelines said one reasonable screening option for women over age 30 is "either the regular Pap test or liquid-based Pap test, plus the HPV DNA test."
The 2006 ASCCP guidelines for managing normal cytology and positive HPV found on screening for women 30 and older "basically reaffirm interim guidance published in 2004 by the ASCCP," Dr. Spitzer says.
As recommended in the 2001 guidelines, Dr. Wilkinson says, the 2006 guidelines "confirm the value of reflex HPV testing in adult women with cervical cytology interpreted as ASC-US."
"Clearly," adds Dr. Wilbur, "using HPV testing after an equivocal or ASC-US Pap smear as part of reflexive testing is a more effective way to triage women into risk groups than a repeat cytology or immediate colposcopy."
In Dr. Wilkinson’s view, "one of the most rewarding things" that has occurred since the last set of guidelines were issued is having ASC-US confirmational studies supporting high-risk HPV testing for the cancer-associated HPV strains. "That is a point ASCCP has been making for some time" in recommending the testing, Dr. Wilkinson says.
Another change in the new guidelines will be "management schemes" geared to different age groups, Dr. Wilbur says. The evidence for that approach comes from ongoing analysis of data from the National Cancer Institute ASC-US/LSIL triage and other studies.
For example, younger women "need to be treated for cervical abnormalities more conservatively than older women," says Dr. Wilbur, pointing to the "risks of pregnancy and low-birth weight babies in women who receive aggressive treatment, such as cone biopsies for relatively low-risk cervical processes."
"Data show that these women have birth complications that pose much greater morbidity to their offspring than the risk of cervical cancer," he says. "That’s one big thing being revisited." And "there’s a whole separate group of the organization looking at adolescents this go-around."
Dr. Wilkinson notes that in the new guidelines, "adolescents, defined as individuals up to 20 years of age, are now considered a ’special population.’" And based on new evidence, the guidelines will recommend "more conservative management and revised followup of adolescents with abnormal cervical cytology in some circumstances," he says.
In addition, "the management of postmenopausal women, and immunosuppressed women who have ASC-US cytology, will be the same as the general population," Dr. Wilkinson says. "There are also some new recommendations on management of adult women with high-grade SIL Pap and/or CIN 2 or CIN 3."
As part of the consensus process, six guidelines committees did the background work for posting proposals on an ASCCP-sponsored Internet-based public bulletin board. "The committees reviewed the literature and looked to see if anything had changed to warrant going in a new direction," says ASCCP executive director Kathy Poole. The ASCCP sent out notices to sponsoring organizations inviting their members to participate in the Internet-based discussion on the committees’ draft recommendations. "That opened the door to a potential 150,000 participants," says Poole, though only about 200 professionals participated. They "tended to be those who publish the most in the area of cervical cytology and histology," she adds.
Before the September consensus conference at the NCI, the ASCCP hosted four teleconferences with the voting delegates to explore the variations in recommendations.
R. Marshall Austin, MD, PhD, a member of the Atypical Glandular Cells Guidelines Committee, says the ASCCP Internet-based discussion forum included a number of proposals for HPV testing without cytology as a preferred "test of cure" for women with previously diagnosed low-grade and high-grade squamous intraepithelial lesions. Those promoting the recommendation for HPV testing without cytology felt the approach to be more efficient, says Dr. Austin, professor of pathology and director of cytopathology at Magee-Womens Hospital of the University of Pittsburgh Medical Center.
The proposal’s detractors made numerous arguments against it, he says, including that "HPV without cytology is not FDA-approved" and "specifically warned against in the package insert." (Related article: "Sticky Business—Using Kits Contrary to Labeling".) Those opposing HPV testing without cytology also pointed out that "some patients with significant lesions will test HPV-negative," says Dr. Austin. He notes that one large metanalysis suggests that "maximum detection of significant lesions can be obtained using FDA-approved co-testing with cytology and HPV testing (DNA with Pap)" (Obstet
Gynecol Surv. 2004; 59:543-553).
Dr. Spitzer notes that practitioners in Europe use HPV testing as a primary screening method. The consensus conference did not address screening protocols because the ASCCP guidelines are geared toward managing women with cervical abnormalities, including those who test positive for HPV. By contrast, the American Cancer Society guidelines address screening for cervical abnormalities and cancer. The American College of Obstetricians and Gynecologists offers a broader set of guidelines encompassing screening and management of cervical abnormalities.
What’s the next step for the ASCCP guidelines? Executive director Poole says once the Steering Committee has its final publication ready for submission, it will decide formally where to submit the guidelines for publication. The organization hopes to follow the "same track" with the consensus guidelines as it did in 2001, Poole says. If it does, the cytology guidelines would be published in the spring, with the histology guidelines following soon after.