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Cervical Cancer Screening
NCCN Clinical Practice Guidelines in Oncology

V.1.2007
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www.nccn.org
NCCN
Practice Guidelines in Oncology v1.2007
Guidelines Index Cervical Screening TOC MS, References
NCCN Cervical Cancer Screening Panel Members

* Edward E. Partridge, MD/Chair W University of Alabama at Birmingham Comprehensive Cancer Center
Mark Morgan, MD W Fox Chase Cancer Center Maria Enriqueta R. Nava, MD Roswell Park Cancer Institute R. Kevin Reynolds, MD W University of Michigan Comprehensive Cancer Center Diljeet K. Singh, MD W Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy Karen Smith-McCune, MD, PhD W UCSF Comprehensive Cancer Center Nelson Teng, MD, PhD W Stanford Comprehensive Cancer Center Cornelia Liu Trimble, MD W The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
* Fidel Valea, MD Duke Comprehensive Cancer Center
Nadeem Abu-Rustum, MD W Memorial Sloan-Kettering Cancer Center Susan Campos, MD Dana-Farber/Brigham and Womens Cancer Center Massachusetts General Hospital Cancer Center Patrick J. Fahey, MD Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University Benjamin E. Greer, MD W Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Sudodh M. Lele, MD UNMC Eppley Cancer Center at The Nebraska Medical Medical Center Richard W. Lieberman, MD University of Michigan Comprehensive Cancer Center Gary H. Lipscomb, MD W St. Jude Childrens Research Hospital/University of Tennessee Cancer Institute
Sharon Wilczynski, MD W City of Hope

* Writing Committee member W Gyn oncology Medical Oncology Internal medicine, including Family practice, Preventive management Pathology
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Version 1.2007, 05-08-07 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
Table of Contents
NCCN Cervical Cancer Screening Panel Members Screening Guidelines for Early Detection of Cervical Cancer (CERVS-1) Initial Findings of Screening Exam (CERVS-3) Follow-up of Screening Exam-Adolescents or Young Women 21 y (CERVS-5) Follow-up of Screening Exam-Adult >21 y (CERVS-6) Findings on Initial Screening/Pap Test, Colposcopy Findings, Cervical Biopsy Findings, Follow-up, Treatment (CERVS-7) Findings at Treatment, Follow-Up Post-treatment (CERVS-10) Follow-up of Cervical Biopsy/Endometrial Biopsy Findings (CERVS-11) Follow-up for Cold-Knife Conization (CERVS-13) Bethesda System 2001 (CERVS-A) Colposcopy During Pregnancy (CERVS-B) Guidelines Index Print the Cervical Cancer Screening Guidelines
For help using these documents, please click here
This manuscript is being updated to correspond with the newly updated algorithm.
Manuscript References
Clinical Trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. To find clinical trials online at NCCN member institutions, click here: nccn.org/clinical_trials/physician.html
NCCN Categories of Consensus: All recommendations are Category 2A unless otherwise specified. See NCCN Categories of Consensus
These guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. 2007.
NCCN
SUMMARY OF GUIDELINES UPDATES

Summary of changes in the 2007 version of the Cervical Cancer Screening guidelines from the 2.2006 version include:
Screening interval: Women who received HPV vaccination should continue cervical cancer screening according to the guidelines. was added (CERVS-2). Screening interval: Frequency of combined cytology and HPV DNA testing should NOT be more often than every 3 years, was clarified by adding, if both tests are negative. (CERVS-2). Initial finding of screening exam: Cervical cytology/Pap test positive for invasive cancer was added (CERVS-3). Follow-up of screening exam: Cervical cytology/Pap test positive for invasive cancer finding was added (CERVS-4). Initial findings of screening exam was separated into Adolescents or young women 21 y and Adult > 21y. Initial findings of screening exam for Adolescents or young women 21 y is new to the algorithm (CERVS-5). Normal was clarified as Negative throughout the algorithm. For treatment of CIN II and CIN III: Preferred was removed from the LEEP procedure (CERVS-7 and CERVS-9). For treatment of CIN II and CIN III: Laser Ablation was removed as a treatment option (CERVS-8). For HSIL, Satisfactory colposcopy: Lesion seen and No lesion seen options were added. In addition, if a lesion is seen, the options of Biopsy and LEEP, if fertility not an issue were added (CERVS-9). For HSIL, Satisfactory colposcopy, No lesion seen: After a negative ECC, the recommendation was changed to Repeat Pap test, colposcopy and ECC in 6 months (CERVS-9). For cervical biopsy negative and CIN I: Review of screening cervical cytology/Pap test was removed (CERVS-9). HSIL, Unsatisfactory colposcopy: See Cervical Biopsy and ECC Findings was replaced with LEEP or CKC (CERVS-9). HSIL, Unsatisfactory colposcopy algorithm was removed from the guideline. Follow-up of: LEEP or CKC or Cryotherapy or Laser excision for CIN was separated into Negative margins for CIN II, III or CIN I with positive or negative margins and Positive margins for CIN II, III and Margin status unknown. (CERVS-10). HPV DNA testing was added as a follow-up option for negative margins (CERVS-10). For Margin status unknown: Follow-up was changed to Cervical cytology/Pap test at 6 mo (CERVS-10). For AGC: < 35 y was clarified as Under 35 y including adolescents (CERVS-11). Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) was added as a risk factor for endometrial cancer (CERVS-11). Nondiagnostic was changed to Unsatisfactory (CERVS-12). Atypical hyperplasia: Consider a referral to gynecologic oncologist was added as an option (CERVS-12). Consider transvaginal ultrasound for endometrial stripe thickness if no other source for AGC has been explained was added to Negative and Unsatisfactory. In addition, D&C was added as an option to Unsatisfactory (CERVS-12). Positive margins: Consider CKC to rule out invasive disease prior to hysterectomy was reclassified as a category 2B (CERVS-13).
Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
UPDATES
NCCN
SCREENING GUIDELINES FOR EARLY DETECTION OF CERVICAL CANCER When to start screening Cervical cancer screening should begin approximately 3 years after the onset of vaginal intercourse. Screening should begin no later than 21 years of age. It is critical that adolescents who may not need a cervical cytology test obtain appropriate preventive health care, including assessment of health risks, contraception and prevention counseling, screening and treatment of sexually transmitted diseases. The need for cervical cancer screening should not be the basis for the onset of gynecologic care.
When to discontinue screening Women at age 70 and older with an intact cervix who have had three or more documented, consecutive, technically satisfactory negative cervical cytology tests, and no abnormal/positive cytology test, within the 10 year period prior to age 70 may elect to cease cervical cancer screening. Screening is recommended for women who have not been previously screened, women for whom information about previous screening is unavailable, and when past screening is unlikely. Women who have a history of cervical cancer, in utero exposure to DES, and/or who are immunocompromised (including HIV+) should continue cervical cancer screening for as long as they are in reasonably good health and do not have a life-limiting chronic condition. Women over the age of 70 should discuss their need for cervical cancer screening with their health care provider based on their individual circumstances, including the potential benefits, harms, and limitations of screening, and make informed decisions about whether to continue screening. Women with comorbid or life-threatening illnesses may forego cervical cancer screening.
Screening Guidelines continued (See CERVS-2)
From Saslow D, Runowicz C, Solomon D, et al., American cancer society guideline for the early detection of cervical neoplasia and cancer. CA: A Cancer Journal for Clinicians 52(6): 342-376, 2002. Reproduced with permission from Lippincott, Williams & Wilkins.
CERVS-1
NCCN
SCREENING GUIDELINES FOR EARLY DETECTION OF CERVICAL CANCER Hysterectomy Screening with vaginal cytology tests after total hysterectomy (with removal of the cervix) for benign gynecologic disease is not indicated. Efforts should be made to confirm and/or document via physical exam and review of the pathology report (when available) that the cervix was completely removed. Women who have had a subtotal hysterectomy should continue cervical cancer screening as per current guidelines. Patients with a history of CIN II-III, or for whom it is not possible to document the absence of CIN II-III prior to or as the indication for the hysterectomy, should be screened until three documented, consecutive, technically satisfactory negative vaginal cytology tests, and no abnormal/positive cytology tests, within a 10 year period are achieved. Women with a history of in utero DES exposure and/or with a history of cervical carcinoma should continue screening after hysterectomy for as long as they are in reasonably good health and do not have a life-limiting chronic condition.
Screening interval After initiation of screening, cervical screening should be performed annually with conventional cervical cytology smears OR every 2 years using liquid-based cytology; at or after age 30, women who have had 3 consecutive, technically satisfactory negative cytology results may be screened every 2-3 years (unless they have a history of in utero DES exposure, are HIV+, or are immunocompromised). HPV DNA testing for primary cervical cancer screening has recently been approved by the FDA for women 30 y of age. It is reasonable to consider that for women age 30 and over, as an alternative to cervical cytology testing alone, cervical screening may be performed every 3 years using conventional or liquid-based cytology combined with a test for DNA for high-risk HPV types. Until more data are available, women who test positive for HPV DNA should continue screening at the discretion of their health care provider. a Frequency of combined cytology and HPV DNA testing should NOT be more often than every 3 years, if both tests are negative. Counseling and education related to HPV infection is a critical need. Women who received HPV vaccination should continue cervical cancer screening according to the guidelines.
See Initial Findings on Screening Exam (CERVS-3)

a FDA approved
HPV testing for high-risk virus types. It is not useful to test for low-risk virus types.
From Saslow D, Runowicz C, Solomon D, et al., American cancer society guideline for the early detection of cervical neoplasia and cancer. CA: A Cancer Journal for Clinicians 52(6): 342-376, 2002. Reproduced with permission from Lippincott, Williams & Wilkins.
CERVS-2
NCCN
INITIAL FINDINGS OF SCREENING EXAM b Visible/suspicious lesion on cervix Cervical cytology/Pap test c,d negative for intraepithelial lesion or malignancy Cervical cytology/Pap test c,d unsatisfactory Cervical cytology/Pap test c,d positive for invasive cancer
See Screening Findings (CERVS-4)
Undetermined significance (ASC-US) Atypical squamous cells (ASC)

Suspicion of high-grade dysplasia (ASC-H)
See Screening Findings Adolescents or Young Women 21 y (CERVS-5) See Screening Findings Adult > 21 y (CERVS-6)
Low-grade squamous intraepithelial lesions (LSIL)
High-grade squamous intraepithelial lesions (HSIL)
Atypical glandular cells (AGC)

b Referral
See Follow-Up of Cervical Biopsy/ Endometrial Biopsy Findings AGC (CERVS-11)
to specialist with oncological expertise for complex clinical situations should be strongly considered. Examples of complex clinical situations include: Atypical glandular cells Adenocarcinoma in-situ Pregnancy Persistent/recurrent dysplasia with desire for fertility preservation c Cervical cytology/Pap test results should be reported using the Bethesda System. See The Bethesda System 2001 (CERVS-A). d Conventional Pap test or thin-layer technology is an acceptable method for primary screening.
CERVS-3
NCCN

FOLLOW-UP OF SCREENING EXAM
SCREENING FINDINGS
Visible lesion on cervix
Biopsy
Cervical cytology/Pap test negative for intraepithelial lesion or malignancy
Screening frequency based on screening guidelines See Screening for Early Detection of Cervical Cancer (CERVS-1)
Cervical cytology/Pap test unsatisfactory
Repeat as soon as practical (3 mo), treat infection if present and indicated
Cervical cytology/Pap test positive for invasive cancer
Biopsy visible lesion; diagnostic excision if no visible lesion
CERVS-4
NCCN
SCREENING FINDINGS

TREATMENT Negative
ADOLESCENTS OR YOUNG WOMEN 21 Y
SCREENING FOLLOW-UP
FOLLOW-UP FINDINGS
Resume screening per guideline (See CERVS-1) Colposcopy g
ASC-US e or LSIL e
Repeat cervical cytology/Pap test at 12 mo
Negative or ASC-US or LSIL
Repeat cervical cytology/ Pap test at 12 mo
ASC-US or LSIL or HSIL
ASC-H or HSIL Negative or CIN l CIN ll/III/NOS f Satisfactory colposcopy CIN ll ASC-H e or HSIL e Colposcopy
Colposcopy g Repeat cervical cytology/Pap test and colposcopy at 6 mo
LEEP or Cyrotherapy or CKC or laser ablation
Repeat cervical cytology/Pap test and colposcopy at 6 mo

LEEP or Cyrotherapy or CKC or laser ablation
CIN lll CIN ll or less Unsatisfactory colposcopy

Perform ECC and cervical biopsy
Repeat cervical cytology/Pap test and colposcopy at 6 mo Repeat cervical cytology/Pap test, colposcopy and ECC at 6 mo LEEP
LEEP
CIN ll, lll, NOS CIN lll
AGC
See Follow-up of Cervial Biopsy/Endometrial Biopsy Findings (CERVS-11)

women 21 y
e HPV testing is not recommended in adolescent or young f May be classified as HSIL on pathological diagnosis g See Colposcopy During Pregnancy (CERVS-B).
CIN= Cervical intraepithelial neoplasia LEEP= Loop electrosurgical excision procedure CKC= Cold-knife conization
CERVS-5
NCCN
ADULT > 21Y

SCREENING FOLLOW-UP

FOLLOW-UP FINDINGS
SCREENING FINDINGS
HPV DNA testing for high risk virus only a (Preferred if available as reflex testing on liquid-based cytology)
Negative
Resume screening per guideline (See CERVS-1) Colposcopy g Repeat cervical cytology/Pap test at 6 mo Colposcopy g Negative Resume screening per guideline (See CERVS-1) Colposcopy g
Positive
Negative ASC-US Repeat cervical cytology/Pap test at 6 mo ASC-US
ASC-US
Immediate colposcopy
LSIL or ASC-H or HSIL
Colposcopy Follow-up See LSIL/ASC-US/ASC-H (CERVS-7) Colposcopy g Colposcopy Follow-up See HSIL (CERVS-9)
AGC
See Follow-up of Cervial Biopsy/Endometrial Biopsy Findings (CERVS-11)
a FDA approved
g See
HPV testing for high-risk virus types. It is not useful to test for low-risk virus types. Colposcopy During Pregnancy (CERVS-B).
CERVS-6
NCCN

CERVICAL BIOPSY FINDINGS

FOLLOW-UP TREATMENT
COLPOSCOPY FINDINGS
Negative
HPV a DNA testing at 12 mo Repeat cervical cytology/Pap test at 6 mo
Negative Positive Negative ASC-US
Resume screening per guideline (See CERVS-1) Colposcopy g Repeat cervical cytology/Pap test at 6 mo Colposcopy g LEEP or Cryotherapy or CKC or Laser ablation LEEP or Cryotherapy or CKC or Laser ablation or Total hysterectomy i
See Follow-up of LEEP, CKC Cryotherapy, or Laser Ablation for CIN (CERVS-10)
Negative ASC-US
CIN l
CIN ll h Satisfactory colposcopy CIN lll

Colposcopy for: LSIL or ASC-US or ASC-H
Microinvasive
CKC See NCCN Cervical Cancer Treatment Guidelines
Cancer Unsatisfactory colposcopy See Cervical Biopsy and ECC Findings (CERVS-8)
a FDA approved
g See
HPV testing for high-risk virus types. It is not useful to test for low-risk virus types. Colposcopy During Pregnancy (CERVS-B). h CIN II may be followed in certain clinical circumstances at the discretion of the physician. i If appropriate for pre-existing pathologic condition or Quality of Life
CERVS-7
NCCN

CERVICAL BIOPSY FINDINGS ENDOCERVICAL CURETTAGE (ECC) FINDINGS

FOLLOW-UP TREATMENT
Negative Negative Negative Repeat cervical cytology/Pap test at 6 mo or Negative CIN l CIN l Unsatisfactory colposcopy for: LSIL or ASC-US or ASC-H; Cervical biopsy and ECC performed Positive CIN ll or lll HPV a DNA testing at 12 mo Positive
Repeat cervical cytology/Pap test at 6 mo
Negative ASC-US Colposcopy g
Resume screening (See CERVS-1) Colposcopy g
ASC-US
LEEP or CKC
Negative CIN ll Positive Negative CIN lll Positive Microinvasion Cancer CIN l, ll, lll CIN l, ll, lll
LEEP or CKC LEEP or CKC LEEP or CKC or Total hysterectomy i LEEP or CKC or Total hysterectomy i after LEEP or CKC for definitive diagnosis CKC
See Follow-up of LEEP, CKC, Cryotherapy for CIN (CERVS-10)
Treat per NCCN Cervical Cancer Treatment Guidelines
aFDA approved gSee
HPV testing for high-risk virus types. It is not useful to test for low-risk virus types. Colposcopy During Pregnancy (CERVS-B). i If appropriate for pre-existing pathologic condition or Quality of Life.
CERVS-8
NCCN

CERVICAL BIOPSY FINDINGS Negative colposcopy/ no biopsy Cervical biopsy negative FOLLOW-UP TREATMENT Negative Perform ECC
CIN I, II, or III
COLPOSCOPY FINDINGS
No lesion seen
Repeat Pap test, colposcopy and ECC in 6 months j LEEP or CKC for definitive diagnosis
Satisfactory colposcopy
CIN l
Biopsy Lesion seen
Repeat Pap test, colposcopy and perform ECC in 6 mo j or Consider LEEP or CKC for definitive diagnosis
CIN ll
LEEP or Cryotherapy or CKC or Laser ablation LEEP or Cryotherapy or CKC or Laser ablation or Total hysterectomy i
See Follow-up of LEEP, CKC, Cryotherapy, or Laser Ablation for CIN (CERVS-10)
Colposcopy for: HSIL

LEEP, if fertility not an issue
CIN lll
Microinvasive
CKC
Cancer
See NCCN Cervical Cancer Treatment Guidelines

See Follow-up of LEEP, CKC, Cryotherapy, or Laser Ablation for CIN (CERVS-10)
Unsatisfactory colposcopy
i If
LEEP or CKC
j Perform
appropriate for pre-existing pathologic condition or Quality of Life vaginal and vulvar colposcopy.
CERVS-9
NCCN

FINDINGS AT TREATMENT

FOLLOW-UP Negative Cervical cytology/Pap test at 12 mo
Resume screening per guideline (See CERVS-1) Colposcopy g (See CERVS-7) Resume screening per guideline (See CERVS-1) Colposcopy g (See CERVS-7)
CIN II, III with negative margins or CIN I with positive or negative margins
ASC-US Negative
HPV DNA a testing at 12 mo Positive
Follow-up of: LEEP or CKC or Cyrotherapy or Laser ablation for CIN
Negative
CIN II, III with positive margins
Cervical cytology/Pap test at 6 mo Consider ECC (category 2B) ASC-US

Reexcision
Resume screening per guideline (See CERVS-1)
Colposcopy g (See CERVS-7)
Cervical cytology/Pap test at 6 mo Margin status unknown Cryotherapy Laser ablation
HPV DNA a testing at 12 mo
a FDA approved
g See
HPV testing for high-risk virus types. It is not useful to test for low-risk virus types. Colposcopy During Pregnancy (CERVS-B).
CERVS-10
NCCN

CERVICAL BIOPSY FINDINGS ECC FINDINGS FOLLOW-UP
Review original cytology if AGC-NOS
FOLLOW-UP OF CERVICAL BIOPSY/ENDOMETRIAL BIOPSY FINDINGS TREATMENT

Repeat cervical cytology every 6 mo until 3 negative
Negative
Negative
Resume screening per guideline (See CERVS-1)

If endometrial biopsy done, see CERVS-12 Resume screening per guideline (See CERVS-1)
Negative Under 35 y including adolescents and no other risk factors
AGC favor neoplasia or AIS CIN I, II, III or AIS
CKC l CKC l
Colposcopy ECC
Negative CIN l
Repeat cervical cytology every 6 mo until 3 negative
Positive CIN I, II, III or AIS Negative CIN ll Positive CIN I, II, III or AIS Colposcopy ECC and endometrial biopsy Negative CIN lll Positive CIN I, II, III or AIS
Adenocarcinoma in situ (AIS)/ microinvasion
CKC l
LEEP or CKC l If CIN I, II, III, see CERVS-10 If endometrial biopsy done, see CERVS-12
AGC
35 y or Endometrial cancer risk factors k or Abnormal bleeding or Atypical glandular endometrial cells
CKC l
LEEP or CKC l
CKC l CKC l
See CERVS-13
Obesity Unopposed estrogen replacement therapy Polycystic ovarian disease Tamoxifen therapy Anovulation Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) l If atypical glandular cells favor neoplasia or adenocarcinoma in situ, follow CKC with endometrial sampling if not yet done.
k Endometrial
Cancer Risk Factors:
Cancer
Treat per NCCN Cervical Cancer Treatment Guidelines
CERVS-11
NCCN
FOLLOW-UP OF CERVICAL BIOPSY/ENDOMETRIAL BIOPSY FINDINGS
Negative
Consider transvaginal ultrasound for endometrial stripe thickness if no other source for AGC has been explained Consider dilatation and curettage (D&C) or Hormonal therapy
Hyperplasia
Endometrial biopsy
Atypical hyperplasia
D&C or Consider referral to gynecologic oncologist
Cancer
See NCCN Uterine Cancer Treatment Guidelines
Unsatisfactory
Consider D&C or Consider transvaginal ultrasound for endometrial stripe thickness if no other source for AGC has been explained in a postmenopausal woman
CERVS-12
NCCN

FOLLOW-UP FOR CKC
Negative margins, fertility desired
Cervical cytology/Pap test ECC every 6 mo until hysterectomy Requires consent/counseling Strongly consider hysterectomy when childbearing completed
Adenocarcinoma in situ (Strongly consider referral to gynecologic oncologist)
Negative margins, fertility not desired
Strongly consider hysterectomy
Positive margins
Repeat CKC at 3 mo if fertility desired Strongly consider hysterectomy when childbearing completed Consider CKC to rule out invasive disease prior to hysterectomy (category 2B)
Cancer
See NCCN Cervical Cancer Treatment Guidelines
CERVS-13
NCCN

BETHESDA SYSTEM 2001
SPECIMEN TYPE: Indicate conventional smear (pap smear) vs. liquid-based vs. other SPECIMEN ADEQUACY Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other quality indicators, eg, partially obscuring blood, inflammation, etc.) Unsatisfactory for evaluation...(specify reason) = Specimen rejected/not processed (specify reason) = Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason) GENERAL CATEGORIZATION (optional) Negative for Intraepithelial Lesion or Malignancy Epithelial Cell Abnormality: See Interpretation/Result (specify squamous or glandular as appropriate) Other: See Interpretation/Result (eg, endometrial cells in a woman 40 y of age) AUTOMATED REVIEW If case examine by automated device, specify device and result ANCILLARY TESTING Provide a brief description of the test methods and report the result so that it is easily understood by the clinician. INTERPRETATION/RESULT NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY (when there is no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result section of the report, whether or not there are organisms or other non-neoplastic findings) ORGANISMS: = Trichomonas vaginalis = Fungal organisms morphologically consistent with Candida spp = Shift for flora suggestive of bacterial vaginosis = Bacteria morphologically consistent with Actinomyces spp. = Cellular changes consistent with Herpes simplex virus OTHER NON-NEOPLASTIC FINDINGS (Optional to report; list not inclusive): = Reactive cellular changes associated with: - inflammation (includes typical repair) Return to Initial Findings - radiation of Screening Exam (CERVS-3) - intrauterine contraceptive device (IUD) = Glandular cells status post hysterectomy Bethesda System 2001 continued on next page. = Atrophy
NCI Bethesda System 2001. Available at: http://bethesda2001.cancer.gov/terminology.html. Accessed January 10, 2003.
CERVS-A 1 of 2
NCCN

BETHESDA SYSTEM 2001
OTHER = Endometrial cells (in a woman 40 y of age) (Specify if negative or intraepithelial lesion) EPITHELIAL CELL ABNORMALITIES SQUAMOUS CELL = Atypical squamous cells - of undetermined significance (ASC-US) - cannot exclude HSIL (ASC-H) = Low grade squamous intraepithelial lesion (LSIL) - encompassing: HPV/mild dysplasia/CIN 1 = High grade squamous intraepithelial lesion (HSIL) - encompassing: moderate and severe dysplasia, CIS/CIN 2 and CIN 3 - with features suspicious for invasion (if invasion is suspected) = Squamous cell carcinoma GLANDULAR CELL = Atypical - endocervical cells (NOS or specify in comments) - endometrial cells (NOS or specify in comments) - glandular cells (NOS or specify in comments) = Atypical - endocervical cells, favor neoplastic - glandular cells, favor neoplastic = Endocervical adenocarcinoma in situ = Adenocarcinoma - endocervical - endometrial - extrauterine - not otherwise specified (NOS) OTHER MALIGNANT NEOPLASMS: (specify) EDUCATIONAL NOTES AND SUGGESTIONS (optional) Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations (references to relevant publications may be included).
Return to Initial Findings of Screening Exam (CERVS-3) Return to Cervical Screening Table of Contents
NCI Bethesda System 2001. Available at: http://bethesda2001.cancer.gov/terminology.html. Accessed January 10, 2003.
CERVS-A 2 of 2
NCCN

COLPOSCOPY DURING PREGNANCY
Recommendations for colposcopy and follow-up are the same as delineated except: No ECC Treatment for CIN (any grade) delayed until after pregnancy Cervical biopsy or colposcopically directed brush cytology is safe during pregnancy Consultation or referral to colposcopist with experience in colposcopy during pregnancy is recommended Diagnostic limited excisional procedure is recommended only if invasion is suspected.
Return to Follow-up of Screening Exam (CERVS-5)
CERVS-B
NCCN
Manuscript
This manuscript is being updated to correspond with the newly updated algorithm.
NCCN Categories of Consensus Category 1: There is uniform NCCN consensus, based on highlevel evidence, that the recommendation is appropriate. Category 2A: There is uniform NCCN consensus, based on lowerlevel evidence including clinical experience, that the recommendation is appropriate. Category 2B: There is nonuniform NCCN consensus (but no major disagreement), based on lower-level evidence including clinical experience, that the recommendation is appropriate. Category 3: There is major NCCN disagreement that the recommendation is appropriate.
All recommendations are category 2A unless otherwise noted.
Overview
Despite a significant decrease in the incidence and mortality of cervical carcinoma in the United States, 9,710 women will be expected to develop the disease in 2006, with 3,700 expected
Manuscript update in progress

Initial Findings
namely, that women should begin screening 3 years after the onset of sexual intercourse or no later than 21 years of age and should undergo an annual Papanicolaou (Pap) test and pelvic examination if using conventional cervical cytology smears or every 2 years using liquid based cytology. In March 2003, FDA approved the use of human papillomovirus (HPV) DNA testing in conjunction with the Pap test for primary cervical cancer screening in women 30 years or older (http://www.fda.gov/bbs/topics/NEWS/2003/NEW00890.html). In women 30 years or older, cervical screening may be performed as an alternative to cervical cytology alone. Combined cytology and HPV DNA testing should not be done more often than every 3 years. After a 30-year old woman at low risk for cervical cancer has had three or more consecutive satisfactory annual examinations with normal findings, the Pap test may be performed less frequently, at the discretion of her physician. The panel also adopted the ACOG (American College of Obstetricians and Gynecologists, 1995) recommendation that women with one or more high-risk factors associated with the development of cervical intraepithelial neoplasia (CIN) or carcinoma may require more frequent Pap tests. The panel further recommends that Pap tests should be reported using the Bethesda System 2001 as shown in CERVS-A. This revision now divides atypical squamous cells into undetermined significance (ASC-US) or suspicion of high-grade dysplasia (ASC-H). The NCCN guideline now reflects this further classification.
3
deaths.1 Since cervical cytology screening is the current method for early detection of this neoplasm, the purpose of the NCCN Cervical Cancer Screening Guidelines is to provide direction for the evaluation and management of cervical cytology.
Pap Test Screening

Frequency
The panel adopted the current recommendations of the American Cancer Society on the initiation and frequency of Pap test screening,2
A biopsy should be performed on any grossly visible or suspicious lesion on the cervix because a Pap test can be reported as negative when invasive cancer is grossly present. If the initial Pap test is negative and the cervix is grossly normal, then subsequent screening should be based on the recommendation for frequency of
MS-1
NCCN
Pap test screening discussed earlier. Pap tests reported as unsatisfactory should be repeated as soon as practical (3 months). Underlying infection, if indicated, should be treated prior to obtaining the subsequent Pap test. Pap tests reported as satisfactory, but limited by or with benign cellular changes, but otherwise negative for epithelial abnormalities, should be repeated at 1 year or sooner if high-risk factors are present.
two repeat tests are normal. Data demonstrate the regression of lowgrade intraepithelial lesions to normal in the majority of cases. If the repeat Pap test at 6 months confirms ASC-US or greater, the patient should then undergo colposcopy. For adult patients the recommendation is to proceed directly to colposcopy. This recommendation for adults is also based on the ALTS trial, which demonstrated that LSIL cytology is best managed by colposcopy initially, because there was no useful triage strategy identified.
7 6
Squamous Epithelial Cell Abnormalities

Atypical Squamous Cells of Undetermined Significance (ASC-US): The guideline offers three options for the management of a cervical cytology that reveals atypical squamous cells of undetermined significance (ASC-US). These options are consistent with the recommendations of the American Society for Colposcopy and Cervical Cytology-sponsored Consensus Conference. The options are: immediate colposcopy or HPV DNA testing for high risk virus with referral for colposcopy if there is a positive identification or repeat cervical cytology with referral for colposcopy in six months if a finding of ASC-US or greater is determined. The inclusion of HPV testing as an option is made on the basis of the results of the ALTS Trial which demonstrated that HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade III and refers about
5 4

Colposcopy
High-Grade Squamous Intraepithelial Lesions (HSIL): The panel recommends that all patients in these categories undergo a colposcopic examination.
half as many women to colposcopy. If two consecutive Pap tests, 6 months apart, are normal, annual screening may be resumed. However, if the repeat Pap test reveals persistent ASC-US or greater, a colposcopic evaluation of the cervix is appropriate. Low-Grade Squamous Intraepithelial Lesion (LSIL) or Atypical Squamous Cells-Suspicion of High Dysplasia (ASC-H): The approach to the management of LSIL or ASC-H depends on the age of the patient. For adolescent patients, the recommendation is to repeat the cervical cytology in six months, with a return to routine screening if
Colposcopy, along with colposcopically directed biopsies, has become the primary method for evaluating women with abnormal Pap tests. During a colposcopic examination, the cervix is viewed through a long focal-length dissecting-type microscope at a magnification of 10 to 16 times. A 4% solution of acetic acid is applied to the cervix before viewing. The coloration induced by the acid and the observance of blood-vessel patterns allow a directed biopsy to rule out invasive disease and determine the extent of preinvasive disease. If the entire squamocolumnar junction of the cervix is visualized (ie, the transformation zone is seen in its entirety), the examination is considered satisfactory and endocervical curettage is unnecessary.
8
LSIL, ASC-US or ASC-H

Women found to have normal/negative histology or CIN I on cervical biopsy after satisfactory colposcopic examination may be followed with a repeat Pap test at 6 months or HPV DNA for high-risk viruses
MS-2
NCCN
at 12 months. Loop electrosurgical excision procedure (LEEP) is not recommended for these patients to avoid potential over-treatment. If negative cervical cytology is found at the six-month exam and at a repeat exam at month 12, a normal screening schedule can be reinstated, reflecting the finding that the majority of these lesions will regress to normal. If ASC-US or greater is found on one of these exams, colposcopy is indicated. For patients followed by HPV DNA at 12 months, a positive exam requires a colposcopy, whereas negative findings permit return to a normal screening schedule. The ALTS Trial suggested that the most efficient test for identifying women with CIN grade II or III after an initial diagnosis of CIN I or less by colposcopy might be an HPV test alone at 12 months.
9 6
If the cervical biopsy reveals CIN II or III, further therapy, consisting of LEEP (preferred), cryotherapy, cold-knife conization (CKC), or laser ablation, is indicated. Total hysterectomy may also be considered an option for CIN III, if indicated for other reasons or for enhancement of quality of life. The panel favored the use of CKC in patients in whom micro invasive cervical cancer was suspected. The LEEP has been associated with a cautery artifact that may compromise the pathologic evaluation of the tissue specimen. A diagnosis of invasive cancer at cervical biopsy requires treatment according to the NCCN Cervical Cancer Guidelines . If the colposcopic examination is unsatisfactory, endocervical curettage should be performed in addition to the directed cervical biopsy. If the cervical biopsy is negative and the endocervical curettage findings are negative or CIN I, repeat cytologic exams at months 6 and 12 or HPV DNA exam at month 12 can be performed. The same strategy as outlined above for a satisfactory colposcopy should be followed. Endocervical curettage with a diagnosis of CIN II or III requires LEEP or CKC for definitive diagnosis.
10

HSIL
A cervical biopsy result of CIN II or III lesions with a positive endocervical curettage finding and an unsatisfactory colposcopic examination also requires a LEEP or CKC to establish a definitive diagnosis. If the endocervical curettage findings are negative, however, treatment can be accomplished with LEEP, CKC or laser ablation. A total hysterectomy may also be a therapeutic option for women with CIN II or III whose diagnosis has been confirmed by LEEP or CKC. CKC is performed for microinvasive biopsy findings. CKC or LEEP can serve as definitive treatment if the lesion is confirmed to be intraepithelial. Ablative therapy with either cryotherapy or laser is inappropriate for those with a positive endocervical curettage finding and unsatisfactory colposcopy. A diagnosis of cancer on cervical biopsy, LEEP or CKC requires treatment according to the NCCN Cervical Cancer Guidelines .
All women with a diagnosis of HSIL on a Pap test require colposcopic evaluation, followed up by a directed biopsy if a lesion is seen. For patients with a negative or CIN I biopsy combined with a negative endocervical curettage finding, screening cervical cytology or Pap test needs to be reviewed. When HSIL is indicated on review or if the slides are not available, LEEP or CKC should be considered for definitive diagnosis. If re-exam of the specimen reveals ASC-US or greater, the patient should be managed as appropriate for these lesions. The same review procedures are recommended for those with cervical biopsy indicating a negative finding or CIN I. A diagnosis of CIN II or III requires treatment with LEEP (preferred), cryotherapy, CKC or laser ablation, with total hysterectomy being a consideration if the lesion is CIN III and other indications for hysterectomy are present. If no biopsy is performed or colposcopy result is normal, endocervical curettage (ECC) should be performed. All
MS-3
NCCN
women with a diagnosis of HSIL on a Pap test and an unsatisfactory colposcopic examination require LEEP or CKC to establish a definitive diagnosis if the result of endocervical curettage is positive (CIN I, II, or III). Again, CKC should be performed for microinvasive biopsy findings and any confirmed invasive cancers need the treatment according to the NCCN Cervical Cancer Guidelines.
Follow-up after treatment of CIN

After definitive treatment of CIN with either LEEP or CKC (leaving clear margins), or ablative therapy with cryotherapy or laser (with the margins status unknown), the patient should have an initial follow-up Pap test at 6 months. If the repeat Pap test at 6 months is normal, the patient may resume annual Pap test screening. An ASCUS or greater finding on a Pap test at 6 months post-treatment requires management as outlined above for each of these lesions. Patients undergoing LEEP or CKC and found to have CIN I extending to the margin of excision should undergo a repeat Pap test in 6 months, with consideration of ECC (category 2B). If the repeat test is negative, annual Pap testing may be resumed. However, if the original LEEP or CKC diagnosis revealed CIN II or III at the margin, the patient may undergo a cervical cytology at 6 months, with an accompanying ECC (category 2B) or undergo reexcision. Follow-up is based on the cervical cytology: if negative, routine testing can be resumed; if indicating ASC-US or greater, management should proceed as recommended for these lesions.
patients with a finding of AGC on a Pap test and who are less than 35 years of age should undergo colposcopy and endocervical curettage. Patients 35 years of age or older with a cervical cytology revealing atypical glandular endometrial cells or abnormal bleeding, or endometrial cancer risk factors (eg, obesity, estrogen replacement therapy, polycystic ovarian syndrome, tamoxifen therapy, or anovulation) should also undergo endometrial biopsy along with colposcopy and endocervical curettage as part of their initial evaluation. If the result of the endometrial biopsy is negative, no further evaluation of the endometrium is necessary. If the endometrial biopsy result is hyperplasia a uterine dilatation and curettage (D&C) or hormone therapy may be considered. Patients with atypical hyperplasia on biopsy should undergo a dilation and curettage. For patients with nondiagnostic endometrial biopsy results, repeat biopsy is considered depending on cervical biopsy findings, or transvaginal ultrasound is performed for endometrial stripe thickening. A diagnosis of endometrial cancer requires treatment according to the NCCN Uterine Cancer Guidelines. If the endocervical curettage and the cervical biopsy results are negative, the original cervical cytology should be reviewed. If the interpretation is atypical glandular cells-nonspecific (AGC-NOS), the patient can be followed with cervical cytology every 6 months until three are negative. If the re-interpretation is atypical glandular cells (AGC) favor neoplasia or adenocarcinoma in situ (AIS), CKC should be performed. If cervical biopsy or endocervical curettage is remarkable for CIN (I, II, or III) or for adenocarcinoma in situ (AIS), further evaluation by CKC is indicated. However, a patient with an adequate colposcopic examination, a cervical biopsy revealing CIN I, and a normal endocervical curettage may be managed conservatively with a
Atypical Glandular Cells (AGC)

The finding of AGC on a Pap test is associated with a clinically significant lesion in 45% of patients, including CIN, cervical adenocarcinoma in situ, and endometrial cancer. For this reason, all
11
MS-4
NCCN
repeat Pap test every 6 months until 3 negative tests are obtained. For patients with cervical biopsy findings of CIN II or III but a negative ECC result, LEEP or CKC is recommended. The panel felt that most patients with a Pap test revealing AGC and an abnormal cervical biopsy result or endocervical curettage should undergo CKC to both confirm the diagnosis and serve as potential treatment. The use of LEEP in patients with adenocarcinoma in situ has been associated with an increased incidence of positive margins of excision in the tissue specimen. For this reason, CKC is the preferred diagnostic procedure in patients at risk for adenocarcinoma in situ or micro invasion. The choice of treatment for adenocarcinoma in situ diagnosed by CKC depends on the patient's desire for fertility. The definitive treatment for adenocarcinoma in situ is hysterectomy. Patients desiring to preserve fertility, and who have a cold-knife conization specimen with negative margins of excision, may be followed conservatively by repeat Pap test and endocervical curettage at 6 months and then cervical cytology every 6 months until hysterectomy. Hysterectomy should be strongly considered when childbearing is completed. However, clear margins of excision do not rule out persistent adenocarcinoma in situ, as approximately 30% of patients have been found to have residual disease on subsequent hysterectomy. If cold-knife conization margins are positive for abnormal glandular cells, strong consideration should be given to performing a hysterectomy. An alternative treatment would be a repeat cold-knife conization at 3 months. If a patient delays hysterectomy until childbearing is complete, CKC should be considered to rule out invasive disease prior to the hysterectomy.
13 12
Finally, patients with invasive adenocarcinoma on cervical biopsy, endocervical curettage, cold-knife conization, or endometrial biopsy should undergo treatment according to the NCCN Cervical Cancer Guidelines or NCCN Uterine Cancer Guidelines .
Colposcopy During Pregnancy

During pregnancy, the recommendations for colposcopy and followup are the same as outlined previously, with the following exceptions. Cervical biopsy or colposcopically directed brush cytology is safe during pregnancy, however, to avoid possible disruption of the pregnancy, endocervical curettage should not be performed. Treatment for CIN (any grade) should be delayed until after the pregnancy. In the case of biopsy-proven CIN II or III in early pregnancy, a repeat colposcopy should be considered later in the pregnancy to rule out progression of the lesion. Since colposcopic evaluation in pregnant women can be problematic, consultation with or referral to an experienced colposcopist should be considered. Diagnostic limited excisional procedure is recommended only if invasive cancer is suspected.
Disclosures for the NCCN Cervical Screening Guideline Panel At the beginning of each panel meeting to develop NCCN guidelines, panel members disclosed financial support they have received in the form of research support, advisory committee membership, or speakers' bureau participation. The panel had nothing to disclose. Some panel members do not accept any support from industry. The panel did not regard any potential conflicts of interest as sufficient reason to disallow participation in panel deliberations by any member.
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References
1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2006. CA Cancer J Clin 2006;56:106-130. 2. Saslow D, Runowicz C, Solomon D et al. American cancer society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342-362. 3. Solomon D, Davey D, Kurman R et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287:2114-2119. 4. Wright TC Jr, Cox J, Massad LS et al. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129.
8. Naumann RW, Crispens MA, Alvarez RD et al. Treatment of cervical dysplasia with large loop excision of the transformation zone: Is endocervical curettage necessary? South Med J 1996;89:961-965. 9. Guido R, Schiffman M, Solomon D, Burke L for the ASCUS LSIL Triage Study (ALTS) Group. Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: A two-year prospective study. Am J Obstet Gynecol 2003;188:1401-1405. 10. Naumann RW, Bell MC, Alvarez RD et al. LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol 1994;55:224-228. 11. Veljovich DS, Stoler MH, Anderson WA et al. Atypical glandular cells of undetermined significance: A five-year retrospective histopathologic study. Am J Obstet Gynecol 1998;179:382-390. 12. Azodi M, Chambers SK, Rutherford TJ et al. Adenocarcinoma in situ of the cervix: Management and outcome. Gynecol Oncol 1999;73:348-353. 13. Wolf JK, Levenback C, Malpica A et al. Adenocarcinoma in situ of the cervix: significance of cone biopsy margins. Obstet Gynecol 1996;88:82-86.
5. The ASCUS-LSIL Triage Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 2003;188:1383-1392.
6. Holowaty P, Miller AB, Rohan T et al. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999;91:252-258.
7. The ASCUS-LSIL Triage Study (ALTS) Group. A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 2003;188:1393-1400.
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Cervical Cancer Screening

NCCN Clinical Practice Guidelines in Oncology

Cervical Cancer Screening

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

NCCN Cervical Cancer Screening Panel Members

Sharon Wilczynski, MD W City of Hope

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

SUMMARY OF GUIDELINES UPDATES

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

Screening Guidelines continued (See CERVS-2)

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

See Initial Findings on Screening Exam (CERVS-3)

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

See Screening Findings (CERVS-4)

Undetermined significance (ASC-US) Atypical squamous cells (ASC)

Low-grade squamous intraepithelial lesions (LSIL)

High-grade squamous intraepithelial lesions (HSIL)

Atypical glandular cells (AGC)

See Follow-Up of Cervical Biopsy/ Endometrial Biopsy Findings AGC (CERVS-11)

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

Visible lesion on cervix

Cervical cytology/Pap test negative for intraepithelial lesion or malignancy

Cervical cytology/Pap test unsatisfactory

Repeat as soon as practical (3 mo), treat infection if present and indicated

Cervical cytology/Pap test positive for invasive cancer

Biopsy visible lesion; diagnostic excision if no visible lesion

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

ADOLESCENTS OR YOUNG WOMEN 21 Y

Resume screening per guideline (See CERVS-1) Colposcopy g

Repeat cervical cytology/Pap test at 12 mo

Negative or ASC-US or LSIL

Repeat cervical cytology/ Pap test at 12 mo

ASC-US or LSIL or HSIL

Colposcopy g Repeat cervical cytology/Pap test and colposcopy at 6 mo

LEEP or Cyrotherapy or CKC or laser ablation

Repeat cervical cytology/Pap test and colposcopy at 6 mo

CIN lll CIN ll or less Unsatisfactory colposcopy

CIN ll, lll, NOS CIN lll

See Follow-up of Cervial Biopsy/Endometrial Biopsy Findings (CERVS-11)

Practice Guidelines in Oncology v1.2007

Cervical Cancer Screening

Guidelines Index Cervical Screening TOC MS, References

Negative ASC-US Repeat cervical cytology/Pap test at 6 mo ASC-US

LSIL or ASC-H or HSIL

See Follow-up of Cervial Biopsy/Endometrial Biopsy Findings (CERVS-11)

Practice Guidelines in Oncology v1.2007