The Society for Lower Genital Tract Disorders Since 1964

The society for lower genital tract disorders since 1964.

Updated Consensus Guidelines for Managing Abnormal Cervical Cancer Screening Tests and Cancer Precursors

American Society for Colposcopy and Cervical Pathology Reprinted – August 2014 Introduction conference held at the National Institutes of Health in cervical precancer. Since then, considerable new informa- September 2012. This report provides updated recommenda- tion has emerged about management of young women, and Cytology tions for managing women with cytological abnormalities. the impact of treatment for precursor disease on pregnancy A more comprehensive discussion of these recommendations outcomes. Progress has also been made in our understanding Since the publication of the 2006 consensus guidelines, new and their supporting evidence was published in the Journal of the management of women with adenocarcinoma in-situ, cervical cancer screening guidelines have been published of Lower Genital Tract Disease and Obstetrics and Gynecology also a human papillomavirus (HPV)—associated precursor and new information has become available which includes and is made available on the ASCCP website at www.asccp.org. lesion to invasive cervical adenocarcinoma. Therefore, in key cervical cancer screening and follow up, and cervical 2012 the ASCCP, together with its partner organizations, precancer management data over a nine year period among Histopathology reconvened the consensus process of revising the guide- more than 1 million women cared for at Kaiser Permanente Appropriate management of women with histo-pathologically lines. This culminated in the September 2012 Consensus Northern California. Moreover, women under age 21 are no diagnosed cervical precancer is an important component of Conference held at the National Institutes of Health. This re- longer receiving cervical cancer screening and cotesting cervical cancer prevention programs. Although the precise port provides the recommendations developed for managing with high-risk HPV type assays, and cervical cytology is being number of women diagnosed with cervical precancer each women with cervical precancer. A summary of the guidelines used to screen women 30 years of age and older. year in the U.S. is not known, it appears to be a relatively themselves–including the recommendations for manag- Therefore, in 2012 the American Society for Colposcopy and common occurence. In 2001 and 2006, the American Society ing women with cervical cytological abnormalities — are Cervical Pathology (ASCCP), together with its 24 partner for Colposcopy and Cervical Pathology and 28 partner published in JLGTD and Obstetrics & Gynecology. professional societies, Federal agencies, and international professional societies, federal agencies, and international organizations, began the process of revising the 2006 organizations, convened processes to develop and update management guidelines. This culminated in the consensus consensus guidelines for the management of women with

Although the guidelines are based on evidence whenever The 2001 Bethesda System terminology is used for cytological is not equivalent to histopathological CIN2,3. The current possible, for certain clinical situations limited high-quality classification. This terminology utilizes the terms low-grade guidelines expand clinical indications for HPV testing based evidence exists. In these situations the guidelines are squamous intraepithelial lesion (LSIL) and high-grade on studies using FDA-approved, validated HPV assays. based on consensus expert opinion. Guidelines should never squamous intraepithelial lesion (HSIL) to refer to low-grade Management decisions based on results using HPV tests be a substitute for clinical judgment. Clinical judgment should lesions and high-grade cervical cancer precursors respec- not similarly validated may not result in outcomes intended always be used when applying a guideline to an individual tively. For managing cervical precancer, the histopathological by these guidelines. HPV testing should be restricted to patient since guidelines may not apply to all patient-related classification is two-tiered applying the terms cervical high-risk (oncogenic) HPV types. Testing for low-risk (non- situations. Finally, both clinicians and patients need to intraepithelial neoplasia grade 1 (CIN1) to low-grade lesions oncogenic) HPV types has no role in evaluating women with recognize that while most cases of cervical cancer can be and CIN2,3 to high-grade lesions. If using the 2012 Lower abnormal cervical cytological results. Therefore, whenever prevented through a program of screening and management Anogenital Squamous Terminology (LAST), CIN1 is equivalent “HPV testing” is mentioned in the guidelines, it refers to of cervical precancer, no screening or treatment modality is to histopathological LSIL and CIN2,3 is equivalent to histo- testing for high-risk (oncogenic) HPV types only. 100% effective and invasive cervical cancer can develop in pathological HSIL. Please note that cytological LSIL is not women participating in such programs. equivalent to histopathological CIN1 and cytological HSIL

Comments Unsatisfactory Cytology

Unsatisfactory Cytology HPV unknown HPV negative HPV positive (any age) (age ≥30) (age ≥30)

Repeat Cytology after 2-4 months Colposcopy

Abnormal Unsatisfactory Nega tive

Routine screening (HPV-/unknown)

Manage per ASCCP or Guideline Cotesting @ 1 year (HPV+)

Ages 21-29† Age ≥ 30

HPV Unknown HPV Negative

HPV Testing Repeat Cytology Preferred @ 3 years Acceptable HPV Positive or Cytology & HPV Test Genotyping @1 year

Routine Screening Manage per ASCCP Guideline * Negative for intraepithelial lesion or malignancy † HPV testing is unacceptable for screening women ages 21-29 years

NILM but EC/TZ Absent Normal Cytology/HPV Positive

Management of Women ≥ Age 30, who are Cytology Negative, but HPV Positive

Repeat Cotesting @ 1 year HPV DNA Typing Acceptable Acceptable

Cytology Negative ≥ ASC HPV 16 or 18 Positive HPV 16 and 18 Negative and or HPV Negative HPV Positive

Repeat Cotesting Colposcopy @ 1 year Repeat Cotesting @ 3 years

Manage per Manage per ASCCP Guideline ASCCP Guideline

Repeat Cytology HPV Testing @ 1 year Preferred Acceptable

Negative > ASC HPV Positive HPV Negative (managed the same as women with LSIL)

Routine Colposcopy Screening† Endocervical sampling preferred in women Repeat Cotesting with no lesions, and those with inadequate @ 3 years colposcopy; it is acceptable for others

* Management options may vary if the woman is pregnant or ages 21-24 Manage per † Cytology at 3 year intervals ASCCP Guideline

ASC-US ASC-US or LSIL: Age 21-24

Management of Women Ages 21-24 years with either Atypical Squamous Cells of Undetermined Significance (ASC-US) or Low-grade Squamous Intraepithelial Lesion (LSIL)

Repeat Cytology @ 12 months HPV Positive Reflex HPV Testing Acceptable for ASC-US only Preferred

Negative, ASC-US ASC-H, AGC, HSIL or LSIL HPV Negative

Repeat Cytology Routine @ 12 months Screening

Negative x 2 > ASC Colposcopy Routine Screening

LSIL with negative HPV test LSIL with no HPV test LSIL with positive HPV test among women > 30 with cotesting

Preferred Acceptable Repeat Cotesting @ 1 year Colposcopy ≥ ASC Non-pregnant and no lesion identified Endocervical sampling “preferred” Cytology Negative or Inadequate colposcopic examination Endocervical sampling “preferred" and HPV positive Adequate colposcopy and lesion identified Endocervical sampling “acceptable” HPV Negative

No CIN2,3 CIN2,3 Repeat Cotesting @ 3 years

* Management options may vary if the woman is pregnant or ages 21-24 years Manage per Manage per † Management women ages 25-29 as having LSIL ASCCP Guideline ASCCP Guideline

with no HPV test

LSIL LSIL Pregnant Woman

Management of Pregnant Women with Low-grade Squamous Intraepithelial Lesion (LSIL)

Colposcopy Defer Colposcopy Preferred (Until at least 6 weeks postpartum) Acceptable

No CIN2,3* CIN2,3

Manage per * In women with no cytological, histological, or Postpartum Follow-up ASCCP Guideline colposcopically suspected CIN2,3 or cancer

Colposcopy Regardless of HPV status

No CIN2,3 CIN2,3

Manage per Manage per ASCCP Guideline ASCCP Guideline

* Management options may vary if the woman is ages 21-24

ASC-H ASC-H and HSIL: Age 21–24

Management of Women Ages 21-24 yrs with Atypical Squamous Cells, Cannot Rule Out High Grade SIL (ASC-H) and High-grade Squamous Intraepithelial Lesion (HSIL)

Colposcopy Immediate loop electrosurgical excision is unacceptable

No CIN2,3 CIN2,3 Two Consecutive Observation with Cytology Negative Colposcopy & Cytology* High-grade colposcopic Results @ 6 month intervals for up to 2 years or and lesion HSIL Persists for 1 year No High-grade Colposcopic Other HSIL Abnormality Results Persists for 24 months with Biopsy no CIN2,3 identified

Routine Manage per Screening Diagnostic CIN2,3 ASCCP Guideline Manage per Excisional for Young Women (If no CIN2,3, * If colposcopy is adequate and endocervical ASCCP Guideline Procedure† with CIN2,3 sampling is negative. Otherwise a diagnostic continue observation) excisional procedure is indicated. © Copyright, 2013, American Society for Colposcopy and Cervical Pathology. All rights reserved. † Not if patient is pregnant Management of Women with High-grade Squamous Intraepithelial Lesions (HSIL)*

I mmediate Loop Co lposcopy Electrosurgical Excision † Or with endocervical assessment

No CIN2,3 CIN2,3

Manage per * Management options may vary if the woman is pregnant, postmenopausal, or ages 21-24 ASCCP Guideline † Not if patient is pregnant or ages 21-24

HSIL AGC

Initial Workup of Women with Atypical Glandular Cells (AGC)

All subcategories Atypical Endometrial Cells (except atypical endometrial cells)

Colposcopy with endocervical sampling Endometrial and and Endometrial sampling (if > 35 yrs or at risk for endometrial neoplasia*) Endocervical Sampling

No Endometrial Pathology

* Includes unexplained vaginal bleeding or conditions suggesting chronic anovulation Colposcopy

Initial Cytology is Initial Cytology is AGC - NOS AGC (favor neoplasia) or AIS

CIN2+ but no No CIN2+, AIS or Cancer No Invasive Disease Glandular Neoplasia

Cotest Manage per Diagnostic @ 12 & 24 months ASCCP Guideline Excisional Procedure* Both Negative Any Abnormality

Cotest * Should provide an intact specimen with interpretable margins. Colposcopy Concomitant endocervical sampling is preferred 3 years later

AGC Subsequent Management CIN1 Preceded by Lesser Abnormalities

Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia — Grade 1 (CIN1) Preceded by “Lesser Abnormalities” * †

Follow-up without Treatment * “Lesser abnormalities” include ASC-US or LSIL Cytology, HPV 16+ or 18+, and persistent HPV Cotesting @ 12 months > ASC or HPV Positive † Management options may vary if the woman is pregnant or ages 21-24. HPV Negative Colposcopy ‡ Cytology if age <30 years, cotesting and if age ≥30 years Cytology Negative ∞ Either ablative or excisional methods. Excision preferred if colposcopy inadequate, positive ECC, or Age appropriate‡ retesting No CIN CIN2,3 CIN1 previously treated. 3 years later

Cytology Negative +/- If persists for Follow-up or HPV Negative Manage per Treatment ∞ ASCCP Guideline at least 2 years Routine Screening‡ © Copyright, 2013, American Society for Colposcopy and Cervical Pathology. All rights reserved. Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia — Grade 1 (CIN1) Preceded by ASC-H or HSIL Cytology

Diagnostic Review of cytological, Cotesting Or Excision Or histological, and @ 12 & 24 months* Procedure† colposcopic findings

HPV Negative HPV Positive HSIL and or Any cytology at either visit Manage per Cytology Negative abnormality ASCCP Guideline at both visits except HSIL for revised diagnosis

* Only if colposcopy was adequate and endocervical sampling is negative Age-specific † Colposcopy Except in special populations (may include pregnant women and those ages 21-24) Retesting ‡ Cytology if age < 30, cotesting if age ≥ 30 years @ 3 years‡

CIN1 Preceded by ASC-H or HSIL CIN1: Age 21-24

Management of Women Ages 21-24 with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia — Grade 1 (CIN1) After ASC-US or LSIL After ASC-H or HSIL

Repeat Cytology @ 12 months

< ASC-H or HSIL > ASC-H or HSIL Manage per ASCCP Guideline for Women Ages 21-24 with ASC-H or HSIL Repeat Cytology using postcolposcopy pathway for @ 12 mos No CIN2,3

Negative > ASC Colposcopy

Routine Screening © Copyright, 2013, American Society for Colposcopy and Cervical Pathology. All rights reserved. Management of Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia — Grade 2 and 3 (CIN2,3)*

Inadequate Colposcopy or * Management options will Adequate Colposcopy Recurrent CIN2,3 or vary in special circumstances Endocervical sampling is CIN2,3 or if the woman is pregnant or ages 21-24 † † If CIN2,3 is identified at the Either Excision or Diagnostic Excisional margins of an excisional Ablation of T-zone* Procedure † procedure or post-procedure ECC, cytology and ECC at 4-6mo is preferred, but repeat Cotesting excision is acceptable and @ 12 & 24 months hysterectomy is acceptable if re-excision is not feasible. 2x Negative Results Any Test Abnormal

Repeat cotesting @ 3 years Colposcopy With endocervical sampling

CIN2,3 Management CIN2,3 in Young Women

Management of Young Women with Biopsy-confirmed Cervical Intraepithelial Neoplasia — Grade 2,3 (CIN2,3) in Special Circumstances*

Observation — Colposcopy & Cytology* Treatment using Excision @ 6 month intervals for 12 months or Ablation of T-zone*

2x Cytology Negative Colposcopy Worsens or and Normal Colposcopy High-grade Cytology or Colposcopy CIN3 or CIN2,3 persists for 24 months Persists for 12 Months Cotest Either Test @ 1 year Abnormal Repeat Colposcopy/Biopsy Treatment Recommended Recommended Both Tests Negative

Cotest @ 3 years * Either treatment or observation is acceptable, provided colposcopy is adequate. When CIN2 is specified, observation is preferred. When CIN3 is specified, or colposcopy is inadequate, treatment is preferred.

Hysterectomy Conservative Management Preferred Acceptable if future fertility desired

Margins Involved or Margins Negative ECC Positive

Re-excision Re-evaluation* Long-term Recommended @ 6 months Follow-up Acceptable

* Using a combination of cotesting and colposcopy with endocervical sampling

AIS Management LAST Terminology

Interim Guidance for Managing Reports using the Lower Anogenital Squamous Terminology (LAST) Histopathology Diagnoses

Low Grade Squamous High Grade Squamous Intraepithelial Lesion Intraepithelial Lesion (LSIL)* (HSIL)*

Manage like Manage like CIN1 CIN2,3

* Histopathology results only © Copyright, 2013, American Society for Colposcopy and Cervical Pathology. All rights reserved. Definitions Terms Utilized in the Consensus Guidelines Acknowledgments These guidelines were developed with funding from the American Society for Colposcopy and Cervical Pathology (ASCCP). The contents are solely the responsibility of the n Colposcopy is the examination of the cervix, vagina, n Diagnostic excisional procedure is the process of authors and the ASCCP. and, in some instances the vulva, with the colposcope obtaining a specimen from the transformation zone L. Stewart Massad, M.D., Washington University School after the application of a 3-5% acetic acid solution and endocervical canal for histopathological evaluation of Medicine, St. Louis, MO; Mark H. Einstein, M.D., Albert coupled with obtaining colposcopically-directed biop- and includes laser conization, cold-knife conization, Einstein College of Medicine, Bronx, NY; Warner K. Huh, M.D., sies of all lesions suspected of representing neoplasia. loop electrosurgical excision procedure (LEEP), and University of Alabama School of Medicine, Birmingham, AL; loop electrosurgical conization. Hormuzd A. Katki, Ph.D., Division of Cancer Epidemiology and n Endocervical sampling includes obtaining a specimen Genetics, National Cancer Institute, Bethesda, MD; Walter K. for either histopathological evaluation using an n Adequate colposcopy indicates that the entire Kinney, M.D., The Permanente Medical Group, Sacramento, endocervical curette or a cytobrush or for cytological squamocolumnar junction and the margin of any CA; Mark Schiffman, M.D., Diane Solomon, M.D., Division of evaluation using a cytobrush. visible lesion can be visualized with the colposcope. Cancer Prevention, National Cancer Institute, Bethesda, MD; n Endocervical assessment is the process of evaluating n Endometrial sampling includes obtaining a specimen Nicolas Wentzensen, M.D., Division of Cancer Epidemiology the endocervical canal for the presence of neoplasia for histopathological evaluation using an endometrial and Genetics, National Cancer Institute, Bethesda, MD; using either a colposcope or endocervical sampling. aspiration or biopsy device, a “dilatation and curettage” Herschel W. Lawson, M.D., Emory University School of or hysteroscopy. Medicine, Atlanta, GA, on behalf of the 2012 ASCCP Consensus Guidelines Conference All copyright permission requests should be sent to the ASCCP National Office, 1530 Tilco Dr., Ste. C, © Copyright, 2002, 2006, 2013 American Society for Colposcopy and Cervical Pathology. All rights reserved Frederick, MD 21704 ASCCP 1530 Tilco Drive, Suite C Frederick, MD 21704 (301) 733-3640 (telephone) (800) 787-7227 (toll free) (240) 575-9880 (fax)

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