Consensus Guidelines for the Management of Women With Cervical Cytological Abnormalities

OBJECTIVE To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors. PARTICIPANTS A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP). EVIDENCE AND CONSENSUS PROCESS Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting. CONCLUSIONS Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

[1]  R. McCarthy Magee Women's Hospital. , 1985, Food management.

[2]  L. Duska,et al.  Clinical Evaluation of Atypical Glandular Cells of Undetermined Significance on Cervical Cytology , 1998, Obstetrics and gynecology.

[3]  Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. , 1995, American journal of obstetrics and gynecology.

[4]  S. Patni,et al.  A prospective follow up study of women with colposcopically unconfirmed positive cervical smears , 1999, British journal of obstetrics and gynaecology.

[5]  S. Hsueh,et al.  High-risk HPV DNA detection by Hybrid Capture II. An adjunctive test for mildly abnormal cytologic smears in women > or = 50 years of age. , 2000, The Journal of reproductive medicine.

[6]  Mark Sherman,et al.  The 2001 Bethesda System: terminology for reporting results of cervical cytology. , 2002, JAMA.

[7]  N. Hardt,et al.  Do Qualifiers of ASCUS Distinguish Between Low- and High-Risk Patients? , 1999, Acta Cytologica.

[8]  M. Schiffman,et al.  ASCUS LSIL Triage Study (ALTS) Conclusions Reaffirmed: Response to a November 2001 Commentary , 2002, Obstetrics and gynecology.

[9]  L. Lagasse,et al.  The significance of atypical glandular cells on routine cervical cytologic testing in a community-based population. , 2000, American journal of obstetrics and gynecology.

[10]  D. Spiegelhalter,et al.  Conservative treatment of mild/moderate cervical dyskaryosis: long-term outcome , 1992, The Lancet.

[11]  B. Jones,et al.  Quality management in gynecologic cytology using interlaboratory comparison. , 2009, Archives of pathology & laboratory medicine.

[12]  M. Schiffman,et al.  Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. , 2001, Journal of the National Cancer Institute.

[13]  Scott B. Cantor,et al.  COLPOSCOPY FOR THE DIAGNOSIS OF SQUAMOUS INTRAEPITHELIAL LESIONS: A META‐ANALYSIS , 1998, Obstetrics and gynecology.

[14]  T. Wright,et al.  Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy? , 1998, The Journal of family practice.

[15]  M. Mazur,et al.  Papanicolaou Smears by the Bethesda System in Endometrial Malignancy: Utility and Prognostic Importance , 1997, Obstetrics and gynecology.

[16]  B. Jones,et al.  Follow-up of abnormal gynecologic cytology: a college of American pathologists Q-probes study of 16132 cases from 306 laboratories. , 2000, Archives of pathology & laboratory medicine.

[17]  E. P. Dellinger,et al.  Purpose of Quality Standards for Infectious Diseases , 1994 .

[18]  L. Hurley,et al.  Where's the High‐Grade Cervical Neoplasia? The Importance of Minimally Abnormal Papanicolaou Diagnoses , 1998, Obstetrics and gynecology.

[19]  K. Holmes,et al.  USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: introduction. USPHS/IDSA Prevention of Opportunistic Infections Working Group. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  L. Massad,et al.  Biopsy correlates of abnormal cervical cytology classified using the Bethesda system. , 2001, Gynecologic oncology.

[21]  S. Granter,et al.  Papanicolaou smear sensitivity for the detection of adenocarcinoma of the cervix , 2001, Cancer.

[22]  N. Joste,et al.  Bethesda classification of cervicovaginal smears: reproducibility and viral correlates. , 1996, Human pathology.

[23]  D. Bell,et al.  Adenocarcinoma In Situ of the Uterine Cervix , 1992, Obstetrics and gynecology.

[24]  G. Friedell,et al.  Adenocarcinoma in situ of the endocervix , 1953, Cancer.

[25]  D. L. Byrne,et al.  Histological differences between colposcopic-directed biopsy and loop excision of the transformation zone (LETZ): a cause for concern. , 1991, Gynecologic oncology.

[26]  D. Petitti,et al.  The clinical significance of the poor correlation of cervical dysplasia and cervical malignancy with referral cytologic results. , 1999, American journal of obstetrics and gynecology.

[27]  David R. Scott,et al.  Toward objective quality assurance in cervical cytopathology. Correlation of cytopathologic diagnoses with detection of high-risk human papillomavirus types. , 1994, American journal of clinical pathology.

[28]  M. Stoler,et al.  Atypical glandular cells of undetermined significance: a five-year retrospective histopathologic study. , 1998, American journal of obstetrics and gynecology.

[29]  C. S. Geier,et al.  Clinical evaluation of atypical glandular cells of undetermined significance. , 2001, American journal of obstetrics and gynecology.

[30]  J. H. Bennett,et al.  Should all women with cervical atypia be referred for colposcopy: a HARNET study. Harrisburgh Area Research Network. , 1994, The Journal of family practice.

[31]  J. T. Cox,et al.  Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). , 2002, Journal of the National Cancer Institute.

[32]  A. Malpica,et al.  Adenocarcinoma in situ of the cervix: Significance of cone biopsy margins , 1996, Obstetrics and gynecology.

[33]  R. Howells,et al.  How can the incidence of negative specimens resulting from large loop excision of the cervical transformation zone (LLETZ) be reduced? An analysis of negative LLETZ specimens and development of a predictive model , 2000, BJOG : an international journal of obstetrics and gynaecology.

[34]  H W Jones,et al.  Impact of the Bethesda System. , 1995, Cancer.

[35]  C. Redman,et al.  Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears. , 1990, BMJ.

[36]  J. Samet,et al.  Food and Drug Administration , 2007, BMJ : British Medical Journal.

[37]  M A Kish,et al.  Guide to development of practice guidelines. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[38]  M. Read,et al.  Colposcopic Diagnosis and Treatment of Cervical Dysplasia at a Single Clinic Visit: Experience of Low Voltage Diathermy Loop in 1000 Patients , 1991 .

[39]  L. Denny,et al.  Does colposcopically directed punch biopsy reduce the incidence of negative LLETZ? , 1995, British journal of obstetrics and gynaecology.

[40]  M. Henry,et al.  Atypical cervical cytology. Colposcopic follow-up using the Bethesda System. , 1993, The Journal of reproductive medicine.

[41]  G. Orth,et al.  Human Papillomavirus Testing in Women With Mild Cytologic Atypia , 2000, Obstetrics and gynecology.

[42]  J. Shim,et al.  Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. , 1999, Gynecologic oncology.

[43]  R. Hiatt,et al.  Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. , 1999, JAMA.

[44]  P. Schwartz,et al.  Adenocarcinoma in situ of the cervix: management and outcome. , 1999, Gynecologic oncology.

[45]  E. P. Dellinger,et al.  Purpose of quality standards for infectious diseases. Infectious Diseases Society of America. , 1994, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[46]  D. Rimm,et al.  Diagnosis of “ASCUS” in women over age 50 is less likely to be associated with dysplasia , 2001, Diagnostic cytopathology.

[47]  M. Tancer,et al.  Abnormal Cervical Cytology in Pregnancy: A 17–Year Experience , 1993, Obstetrics and gynecology.

[48]  J. Kurinczuk,et al.  The "Inconclusive‐Possible high grade epithelial abnormality" category in papanicolaou smear reporting , 1998, Cancer.

[49]  C. Crum,et al.  LSIL biopsies after HSIL smears. Correlation with high-risk HPV and greater risk of HSIL on follow-up. , 1999, American Journal of Clinical Pathology.

[50]  F. Abreo,et al.  Cytohistologic Correlation Between AGUS and Biopsy-Detected Lesions in Postmenopausal Women , 2000, Acta Cytologica.

[51]  M. Sherman,et al.  Qualification of ASCUS. A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study. , 2001, American journal of clinical pathology.

[52]  M. Chiasson,et al.  Significance of mild cytologic atypia in women infected with human immunodeficiency virus , 1996, Obstetrics and gynecology.

[53]  M. Sherman,et al.  Atypical glandular cells of undetermined significance (AGUS): Interobserver reproducibility in cervical smears and corresponding thin-layer preparations. , 2002, American journal of clinical pathology.

[54]  S. Granter,et al.  Papanicolaou smear sensitivity for adenocarcinoma in situ of the cervix. A study of 34 cases. , 1997, American journal of clinical pathology.

[55]  M. Quinn,et al.  Adenocarcinoma in situ of the uterine cervix: an experience with 100 cases. , 2000, Gynecologic oncology.

[56]  J. Cangiarella,et al.  Clinical significance of atypical glandular cells of undetermined significance in postmenopausal women , 2001, Cancer.

[57]  C Eskridge,et al.  Cervicography Combined With Repeat Papanicolaou Test as Triage for Low‐Grade Cytologic Abnormalities , 1998, Obstetrics and gynecology.

[58]  Jones Ba,et al.  Cervical biopsy-cytology correlation. A College of American Pathologists Q-Probes study of 22 439 correlations in 348 laboratories. , 1996 .

[59]  M. Spitzer,et al.  Indications for cone biopsy: pathologic correlation. , 1998, American journal of obstetrics and gynecology.

[60]  J. Niloff,et al.  Incidence and Predictors of Cervical Dysplasia in Patients With Minimally Abnormal Papanicolaou Smears , 1998, Obstetrics and gynecology.

[61]  B. Jones,et al.  Cervical biopsy-cytology correlation. A College of American Pathologists Q-Probes study of 22 439 correlations in 348 laboratories. , 1996, Archives of pathology & laboratory medicine.

[62]  A. Valdini,et al.  Incidence and evaluation of an AGUS Papanicolaou smear in primary care. , 2001, The Journal of the American Board of Family Practice.

[63]  T. Denehy,et al.  Endocervical Curettage, Cone Margins, and Residual Adenocarcinoma In Situ of the Cervix , 1997, Obstetrics and gynecology.

[64]  C. Crum,et al.  Subclassifying atypical squamous cells in Thin-Prep cervical cytology correlates with detection of high-risk human papillomavirus DNA. , 1999, American journal of clinical pathology.

[65]  L. Tuason,et al.  Results of the clinical evaluation of atypical glandular cells of undetermined significance (AGCUS) detected on cervical cytology screening. , 1996, Gynecologic oncology.

[66]  T. Byers,et al.  Prediction of Cervical Intraepithelial Neoplasia Grade 2–3 Using Risk Assessment and Human Papillomavirus Testing in Women With Atypia on Papanicolaou Smears , 2000, Obstetrics and gynecology.

[67]  T. Wright,et al.  Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears. , 1998, American journal of obstetrics and gynecology.

[68]  Helen H Wang,et al.  Significance of a diagnosis of atypical squamous cells of undetermined significance for Papanicolaou smears in perimenopausal and postmenopausal women , 2001, Cancer.

[69]  M. Hutchinson,et al.  Atypical squamous metaplastic cells , 2001, Cancer.

[70]  R. Zaino,et al.  Variance in the interpretation of cervical biopsy specimens obtained for atypical squamous cells of undetermined significance. , 2000, American journal of clinical pathology.

[71]  L. Koutsky Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. , 2000, Journal of the National Cancer Institute.

[72]  M. Sherman,et al.  The Bethesda System , 1993 .

[73]  C. Holschneider,et al.  A single‐visit cervical carcinoma prevention program offered at an inner city church , 1999, Cancer.

[74]  D. Bell,et al.  Endocervical Glandular Atypia in Papanicolaou Smears , 1992, Obstetrics and gynecology.

[75]  J. Robb The “ASCUS” swamp , 1994, Diagnostic cytopathology.

[76]  G. Sterrett,et al.  Adenocarcinoma in situ of the cervix , 2002, Cancer.

[77]  M. Schiffman,et al.  Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. , 2001, JAMA.

[78]  E. Trimble,et al.  Interim Guidelines for Management of Abnormal Cervical Cytology , 1994 .

[79]  J. L. Benedet,et al.  Colposcopic evaluation of abnormal Papanicolaou smears in pregnancy. , 1987, American journal of obstetrics and gynecology.

[80]  T. Wright,et al.  Comparison of two tests for detecting carcinogenic HPV in women with Papanicolaou smear reports of ASCUS and LSIL. , 1998, Journal of Family Practice.

[81]  E. Manna,et al.  Atypical endocervical glandular cells: Accuracy of cytologic diagnosis , 1995, Diagnostic cytopathology.

[82]  M. Read,et al.  Efficacy and safety of large-loop excision of the transformation zone , 1994, The Lancet.

[83]  W. R. Hart,et al.  Adenocarcinomain Situof the Uterine Cervix: Management and Outcome , 1996 .

[84]  J. Robertson,et al.  Risk of cervical cancer associated with mild dyskaryosis. , 1988, BMJ.

[85]  K. Noller,et al.  Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology. , 1997, Gynecologic oncology.

[86]  Velarde,et al.  One-Session Management of Cervical Intraepithelial Neoplasia: A Solution for Developing Countries. A Prospective, Randomized Trial of LEEP versus Laser Excisional Conization , 1996, Gynecologic oncology.

[87]  G. Giles,et al.  Cervical cytology reported as negative and risk of adenocarcinoma of the cervix: no strong evidence of benefit. , 1995, British Journal of Cancer.

[88]  S. Fleisher,et al.  Atypical glandular cells of undetermined significance (AGUS): Clinical considerations and cytohistologic correlation , 2002, Diagnostic cytopathology.

[89]  J. Robertson,et al.  Cytological changes preceding cervical cancer. , 1994, Journal of clinical pathology.

[90]  A. Farnsworth,et al.  The Reliability of a Cytological Prediction of Cervical Adenocarcinoma In Situ , 1988, The Australian & New Zealand journal of obstetrics & gynaecology.

[91]  T. Rollason Blaustein’s Pathology of the Female Genital Tract , 2003, Springer New York.