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CAP Home > CAP Reference Resources and Publications > CAP TODAY > CAP TODAY 2007 Archive > ASCCP '06 consensus guidelines�what's new and different?
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  ASCCP '06 consensus guidelines—what's
  new and different?

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November 2007
PAP/NGC Programs Review

Teresa M. Darragh, MD
Terence J. Colgan, MD

The long-awaited new recommendations from the American Society for Colposcopy and Cervical Pathology have arrived.

The second ASCCP consensus conference for the management of women with cervical cytological abnormalities and cervical intraepithelial neoplasia was held in Bethesda, Md., in September 2006. The conference addressed management of women with abnormal cervical cancer screening tests and with cervical intraepithelial neoplasia or adenocarcinoma in situ on colposcopic biopsy. With the recent publication of the recommendations from this meeting in the American Journal of Obstetrics and Gynecology and the Journal of Lower Genital Tract Disease, the press embargo has been lifted.

Here, we will highlight key points and summarize changes to the management recommendations. Key points of interest to pathologists are summarized in Table 1.

The second consensus conference was convened for two reasons. First, the management recommendations needed to be simplified. The maze of recommendations from the 2001 conference proved difficult for many to recall and use, except for experts in the field; they were hardly at the fingertips of many clinicians who care for women. Second, since 2001, a wealth of clinical evidence from randomized, controlled studies, particularly from ALTS and the National Cancer Institute's Guanacaste and Portland cohorts, has become available. Thus, simplifying the management recommendations and incorporating our new understanding of HPV-related cervical disease were the prime goals of the 2006 ASCCP consensus conference.

Two fundamental principles guided the revision of the guidelines: assessment of risk and detection of proven cancer precursor lesions. All management recommendations are based on an assessment of the risk for significant cervical disease in a given clinical situation. Women with a similar risk should be managed using a similar or identical method. It was acknowledged that no management strategy can eliminate all risk through absolute assurance that every significant cervical lesion has been detected. Second, cervical cancer screening programs aim to identify and treat true cervical cancer precursors—that is, CIN2, CIN3, and adenocarcinoma in situ. (Though CIN2 is a heterogeneous diagnosis, its inclusion with the management recommendations for CIN3 provides a margin of safety.) Thus, triage to colposcopy or conservative followup via Pap or HPV testing or both is also based on the likelihood of detecting these lesions. CIN1 is essentially evidence of an active HPV infection, the majority of which will spontaneously regress; it is not considered a true precancer, though it may be useful in establishing current and future risk.

The updated guidelines also use high-risk-HPV testing in cervical cancer screening and triage to an increasing degree. The guidelines recommend use of an analytically sensitive and clinically validated HPV test. Only testing for high-risk HPV types is recommended; testing for low-risk HPV types is not applicable to a cancer screening program. The major changes from 2001 to 2006 in the management of women with Pap test abnormalities (that is, triage) and of women with histologically proven abnormalities (on colposcopic biopsy) are summarized here by category of cytologic interpretation, histologic diagnosis, or both. Bethesda terminology is used when referring to cytologic results (for example, LSIL, HSIL) whereas a modified two-tiered CIN classification (CIN1 and CIN2,3) is used for histologic results. Some basic principles apply:

  • Triage to colposcopy or conservative management is based on the risk associated with underlying CIN2+.
  • Post-colposcopy followup evaluation for squamous disease (with or without treatment) is usually at six- and 12-month intervals when using Paps (until two negatives) and in 12 months when using HPV testing (until one negative).
  • During the followup period, the threshold to send a patient to colposcopy is greater than or equal to ASC-US on Pap or a positive HPV test, except in special populations.
  • Adolescents are considered a "special population" for which the management strategies differ from those for women 21 years of age and older.

Atypical squamous cells: ASC-US and ASC-H

No major changes were made in the recommendations for managing women with ASC-US. Reflex high-risk-HPV testing remains the preferred approach when liquid-based cytology is used or an HPV specimen has been co-collected. Women with ASC-US on a screening cytology, who are high-risk-HPV positive, should proceed to colposcopy. It is now recommended that postmenopausal and immunosuppressed (including HIV+) women with ASC-US be managed in the same manner as the general population of women undergoing regular cervical cancer screening. If colposcopic-directed biopsy does not show CIN 2+, then post-colposcopic followup with either Pap at six and 12 months or high-risk-HPV testing at 12 months is acceptable.

Colposcopy remains the recommended management for women with ASC-H on Pap. Data from ALTS demonstrated that over 85 percent of women with ASC-H on Pap were high-risk-HPV positive and about 40 percent of women were found to have CIN2+ on biopsy. Future studies may clarify the utility of high-risk-HPV testing in the management of women with ASC-H in various subgroups—for example, the postmenopausal age group, but there is insufficient evidence at this time to alter the recommendation for colposcopy for all women with ASC-H. If no CIN2,3 is identified at colposcopy, it is acceptable to follow up with Paps at six and 12 months or HPV testing at 12 months. The prior 2001 recommendation for a review of the original, index ASC-H Pap in the absence of biopsy-proven CIN2,3 has been eliminated, since few pathologists are willing to actually "downgrade" an initial ASC-H interpretation.

LSIL and CIN1

Women with LSIL on Pap have approximately the same risk of having biopsy-proven CIN2,3 as those who are ASC-US and high-risk-HPV positive. Consequently, similar management strategies are recommended for both groups—colposcopy. Adolescents and possibly postmenopausal women are exceptions to this rule. Since the prevalence of high-risk-HPV is lower in postmenopausal women, reflex high-risk-HPV testing for LSIL in these women, with triage to colposcopy if HPV positive, is acceptable. The main purpose of colposcopy is the detection of CIN2,3 and cancer.

Our increasing understanding of the natural history of HPV infection and high spontaneous regression rates yields one of the major take-home messages from the new guidelines: It is recommended that all women with CIN1 be observed for up to two years before being treated. This applies to women whose diagnosis of CIN1 was preceded by a Pap showing ASC-US, ASC-H, or LSIL (whether or not they have a satisfactory colposcopy). Followup may consist of high-risk-HPV testing every 12 months or repeat Paps at six- to 12-month intervals. Repeat colposcopy is recommended if followup shows high-risk-HPV+ or ASC-US or worse. If after two years of observation, no CIN2+ is detected and CIN1 persists, either continued followup or treatment is acceptable. For CIN1 preceded by a Pap showing HSIL or atypical glandular cells, more surveillance is recommended, given the higher risk associated with these Pap interpretations. These women may be followed by colposcopy and cytology at six-month intervals for one year, have a diagnostic excisional procedure, or have their findings reviewed with subsequent management based on any revisions. For pregnant women with LSIL, colposcopy may be performed once (rather than every trimester) to exclude high-grade disease or deferred to the postpartum period.

HSIL and CIN 2,3

The principal 2001 recommendations for colposcopy of all women with HSIL and management of CIN 2,3 are unchanged by the 2006 consensus conference. All biopsy-proven CIN 2,3 should be treated (adolescents remain a possible exception). More emphasis was placed on immediate LEEP ("see and treat") as an acceptable initial management option for women with HSIL on Pap, except in special populations. Treatment of CIN 2,3 is deferred during pregnancy, unless cancer is suspected. An option for conservative management of adolescents with CIN2,3 will be discussed later. Many pathologists now use a two-tiered classification for histologic diagnosis of intraepithelial lesions, lumping together CIN2 and CIN3, often by simply using the cytologic term "HSIL" for CIN2,3. This two-tiered diagnostic category of CIN1 and CIN2,3 better reflects our understanding of the natural history of HPV-related lesions—as low-grade mucosal infections and as potential cervical cancer precursors. It also bows to the interobserver variability inherent in these diagnoses. With the exception of managing adolescents with high-grade disease, which will be discussed in the "special populations" section, the lumped diagnostic category of CIN2,3 triggers the appropriate clinical response.

Atypical glandular cells

The basic guidelines for the management of women with the atypical glandular cells, or AGC, of all subcategories and AIS on Pap have not changed. Colposcopy with endocervical sampling is recommended for all (with the exception of women with atypical endometrial cells). If the patient is 35 years of age or older, or less than 35 years with any clinical suggestion of increased risk for endometrial neoplasia, endometrial sampling should also be performed at the time of colposcopy. If atypical endometrial cells were present on the index Pap, endometrial and endocervical sampling are recommended as the initial evaluation; colposcopy can be deferred if no pathology is found. If CIN is identified histologically in this assessment, management follows that specific guideline. If AIS is found, a diagnostic excisional procedure is recommended; ablative therapy is unacceptable. The 2006 management guidelines accept the possibility of using LEEP as an alternative to cold knife cone biopsy and stress that either excisional biopsy technique should be designed to obtain an intact specimen with interpretable margins.

If no CIN2,3, AIS, or cancer is identified, the post-colposcopy management varies by original Pap interpretation. A diagnostic excisional procedure is still recommended for women with Pap showing AGC-favor neoplasia, atypical endocervical cells-favor neoplasia, or adenocarcinoma in situ. Women with AGC, NOS may be managed more conservatively.

While high-risk-HPV testing is still not acceptable for the initial triage of women with AGC of any variety, it is useful in the post-colposcopy followup of women with AGC, NOS in which no CIN2,3 or AIS have been found. Women who are negative for high-risk HPV can be followed less aggressively than those who are high-risk-HPV positive. The high-risk-HPV negative woman may have followup with repeat Pap and HPV testing delayed to 12 months. In contrast, this time interval is shortened to six months if the patient is high-risk-HPV positive. A shortened time interval for followup using cytology only at six-month intervals until four negative Paps is recommended for women with unknown HPV status.

The new guidelines also include comprehensive management recommendations for women with biopsy-confirmed AIS of the cervix. For those in whom future fertility is desired, conservative management by cone or LEEP excision, followed by long-term surveillance, is acceptable. If margins or endocervical sampling at the time of excision are positive, re-excision to ensure negative margins is preferred. However, repeat Pap, HPV testing, colposcopy, and endocervical evaluation at six months is acceptable in this circumstance, too. Whenever the conservative management option is chosen, long-term followup is recommended. For women who have completed childbearing, hysterectomy is the preferred management for AIS found on an excisional procedure.

Special populations: pregnant women, adolescents

Only cervical cancers are treated during pregnancy. For women with low-grade cytologic abnormalities, colposcopy can be deferred until the postpartum period. The goal of colposcopic evaluation of women with HSIL during pregnancy is to rule out invasive cancer; if no cancer is identified, treatment is deferred until the postpartum evaluation. Endocervical curettage is unacceptable during pregnancy.

Adolescents, defined as girls and women less than 21 years of age, have a very high prevalence of HPV infection, low-grade cytologic abnormalities, and CIN1, yet have a very low risk of cervical cancer. The majority of these infections will regress spontaneously and are of little long-term clinical significance. Colposcopy and overtreatment of these transient HPV infections may lead to potential harm. High-risk-HPV testing in this age group is unacceptable because of the high prevalence of transient HPV infection in adolescents.

Adolescents with HSIL on Pap should be sent for immediate colposcopy. Adolescents with either ASC-US or LSIL on Pap should be followed by repeat Pap at 12 and 24 months, and referred to colposcopy only if HSIL or worse is detected at 12 months, or if ASC-US or greater results persist for 24 months. Since the risk of CIN2+ is low, colposcopy is not recommended for the initial management of these low-grade Pap abnormalities in adolescents. HPV testing is not recommended in this group due to high prevalence of infection. Treatment of CIN1 in adolescents is unacceptable. Immediate LEEP (that is, "see and treat") is unacceptable in adolescents. The take-home message regarding cervical cancer screening in adolescents is, Leave adolescents alone.

The pathologic grading of cervical biopsies will play a significant role in managing adolescents with high-grade disease. More and more pathologists are using Bethesda terminology for histologic diagnosis; a two-tiered system more accurately reflects our understanding of HPV-related infection and precancer. However, clinical management in adolescents now depends on a more subtle and nuanced histologic reporting. If CIN2,3 is diagnosed in an adolescent, either observation for up to 24 months or treatment is acceptable, provided the colposcopy is satisfactory. If CIN2 is specified, observation is the preferred approach, though treatment is acceptable. If CIN3 is specified on biopsy or the colposcopy is unsatisfactory, treatment is preferred. This acknowledges, once again, that the histologic diagnosis of CIN2 is a heterogeneous group with high spontaneous regression rates, particularly in adolescents, and that there is poor interobserver reproducibility of this diagnostic category.

The 2006 guidelines acknowledge that although LEEP (loop electrosurgical excisional procedure) has become an important tool in the clinical repertoire, it is not without potential reproductive consequences for our patients. As such, LEEP should be used judiciously to treat high-grade disease, particularly in adolescents and young women of reproductive age. Similarly, see-and-treat is not a recommended management option in adolescents.

High-risk-HPV DNA testing

HPV testing is being used with increasing frequency in cervical cancer screening and in managing HPV-related disease. However, it must be used judiciously to prevent increasing the costs of cervical cancer prevention without reaping its benefits. HPV testing may be used in several clinical scenarios: in screening in conjunction with the Pap in women 30 years and older, in the triage of ASC-US on Pap, in the triage of postmenopausal women with LSIL on Pap, and in the post-colposcopy followup of abnormalities (Table 2).

In 2004, the interim guidance recommendations were proposed for the management of women undergoing cervical screening using high-risk-HPV and Pap testing. These recommendations were adopted at the 2006 consensus conference. Women over 30 years of age, who are Pap negative and HPV negative, may be re-screened at three-year intervals. Women who are Pap negative but HPV positive are re-screened by repeating both tests in 12 months.

High-risk-HPV testing also plays an increasing role in the post-colposcopy management of women with either high-grade squamous or glandular disease. In the standard followup of low-grade abnormalities after colposcopy, it may be used at 12-month intervals, allowing time for spontaneous regression. After diagnostic excisional procedure for either CIN2,3 or AIS, it is used at six- to 12-month intervals, as a test of cure.

In the future, HPV genotyping may play an important role in the triage and management of women with HPV-related disease. HPV 16 and 18 are known as "bad actors" in the disease process, with a higher representation among cervical cancer than other high-risk HPV types. Once these tests become available and gain FDA approval, data may support the triage of HPV-positive women using assays that specifically identify HPV 16 and 18.

Many new and exciting changes are happening in the world of cervical cancer screening. Our understanding of the disease process and risk for cervical cancer indicated by specific abnormalities is expanding. Risk assessment is becoming a guiding force behind our management strategies. In addition, the full impact of the newly approved cervical cancer vaccine, Gardasil, on cervical cancer screening and prevention is still unfolding. Stay tuned.

References

The 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests were published in the American Journal of Obstetrics and Gynecology (2007;197[4];346-355) and the Journal of Lower Genital Tract Disease (2007;11[4];201-222).

The 2006 Consensus Guidelines for the Management of Women with Cervical Intraepithelial Neoplasia or Adenocarcinoma In Situ were published in the American Journal of Obstetrics and Gynecology (2007;197[4]:340-345) and the Journal of Lower Genital Tract Disease (2007;11[4];223-239).

Link to ASCCP Web site for management algorithms and additional information: www.asccp.org.


Dr. Darragh, a member of the CAP Cytopathology Committee, is professor of clinical pathology, Departments of Pathology and Ob/Gyn, University of California San Francisco/Mt. Zion Medical Center, San Francisco. Dr. Colgan, a former member of the Cytopathology Committee, is chief, gynecologic pathology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, and professor, University of Toronto.

 

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