11. Management of glandular abnormalities

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Cervical adenocarcinoma is associated with human papillomavirus (HPVHuman papillomavirus) infection and can be detected by HPV testing.[1] HPV has been identified in an estimated 99.7% of cervical carcinoma specimens.[2] While 70% of squamous cervical cancers are related to oncogenic HPV types 16 and 18 an estimated 78% of adenocarcinomas are related to these two types[3] and the proportion associated with HPV 18 is greater than for squamous cell carcinomas.[4] Glandular abnormalities are also associated with a substantial risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer; in a large US cohort, 33% of HPV-positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. women with a conventional cytology finding of atypical glandular cells developed CIN3 or a higher-grade lesion (CIN3+) and 9% developed cervical cancer within 5 years.[5] Among women with the same cytology finding in whom oncogenic HPV was not detected, 0.93% developed CIN3+ and 0.37% developed cervical cancer.[5] Glandular and squamous lesions commonly coexist,[1] with CIN found in approximately half of women with endocervical adenocarcinoma in situ (AISAdenocarcinoma in situ).[6][7]

In Australia, adenocarcinoma accounts for approximately 25% of cervical carcinomas, while adenosquamous carcinoma accounts for approximately 4%.[8] After an initial decrease from 2.8 new cases per 100,000 women in 1991, the incidence of adenocarcinoma has remained at around 2 new cases per 100,000 women.[8]

Cervical screening based on cytology is less effective in preventing cervical adenocarcinoma than squamous cell carcinomas.[9] Cervical cytology is less sensitive for the detection of glandular lesions than for the detection of squamous intraepithelial lesions and squamous cell carcinoma, due to sampling and interpretation issues.[4] Primary HPV screening has been found to be more effective than cytology for the prevention of adenocarcinoma.[10]

Cytological glandular abnormalities are also associated with polyps, metaplasia and adenocarcinomas of the endometrium, ovary, fallopian tube and other sites, which would not be detected through HPV based cervical screening.[1] The detection and management of these conditions is outside the scope of this guideline.

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The Australian Modified Bethesda System (AMBSAustralian Modified Bethesda System 2004) for reporting glandular abnormalities recognises the following categories (see Chapter 3. Terminology):[9]

  • atypical endocervical cells of undetermined significance/atypical glandular cells of undetermined significance
  • possible high-grade glandular lesion
  • AISAdenocarcinoma in situ
  • adenocarcinoma.

Glandular abnormalities are uncommonly reported on cytology. In Australia, the finding of atypical endocervical/glandular cells of undetermined significance is reported in approximately 0.04% of cytology tests, possible high-grade endocervical glandular lesions in approximately 0.02–0.3%, AISAdenocarcinoma in situ in approximately 0.01%, and adenocarcinoma in fewer than 0.01% of cytology tests.[8]

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Investigational modalities

Issues in the investigation and management of screen-detected glandular abnormalities differ from those for squamous abnormalities. These include the roles of HPV testing, colposcopy and endocervical sampling in the detection and investigation of cytological glandular abnormalities, and the optimal modality of excisional biopsy.

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. may detect minimal cervical changes in women with a cytological prediction of AISAdenocarcinoma in situ.ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. has a low sensitivity for detecting endocervical lesions, and women with endocervical glandular abnormalities on cytology have a significant cancer risk even when colposcopy is normal.[11]

The use of endocervical sampling (by endocervical curettage or cytobrush) in the investigation of glandular abnormalities has been controversial (see Chapter. 7. Colposcopy).[1] Endocervical brushing has higher sensitivity, is better tolerated, and produces fewer insufficient samples than endocervical curettage. However, grading may be more difficult for brush specimens.[1] Although recommended for women with a cytology finding of atypical glandular cells in Canadian and European guidelines,[12][13] endocervical curettage ECCis not frequently practised in Australia and its role has been controversial. It has little place in the management of women with a high probability of neoplasia, but might improve the chance of identifying a glandular lesion when cytology suggests a possible high-grade glandular abnormality.[9] Guidelines for the pre-renewal National Cervical Screening Program (NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.) advised that it could be considered as part of conservative management.[9]

The use of excisional biopsy modalities other than cold-knife cone in the investigation of cervical glandular abnormalities remains controversial (see Modalities of treatment in Chapter 7. ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities.).


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  1. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al ;American Society for ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. and Cervical Pathology Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013 Apr;17(5 Suppl 1):S1-S27 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23519301.
  2. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999 Sep;189(1):12-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10451482.
  3. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007 Feb 15;120(4):885-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17131323.
  4. 4.04.1 Wilbur DC, Chhieng DC, Guidos B, Mody DR. Epithelial abnormalities: glandular. In: Nayar R, Wilbur DC (Eds).The Bethesda system for reporting cervical cytology. Definitions, criteria and exploratory notes. 3rd ed.Springer; 2015.
  5. 5.05.1 Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Five-year risks of CIN 3+ and cervical cancer among women with HPV-positive and HPV-negative high-grade Pap results. J Low Genit Tract Dis 2013 Apr;17(5 Suppl 1):S50-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23519305.
  6. Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, Sorosky JI. Dysplasia associated with atypical glandular cells on cervical cytology. Obstet Gynecol 2005 Mar;105(3):494-500 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15738014.
  7. Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Relationship of atypical glandular cell cytology, age, and human papillomavirus detection to cervical and endometrial cancer risks. Obstet Gynecol 2010 Feb;115(2 Pt 1):243-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20093895.
  8. Australian Institute of Health and Welfare. Cervical screening in Australia 2012–2013. Cancer series no. 93. Cat. no. CAN 91. Canberra: AIHWAustralian Institute of Health and Welfare; 2015 Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129550872.
  9. National Health and Medical Research Council. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRCNational Health and Medical Research Council; 2005.
  10. Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014 Feb 8;383(9916):524-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24192252.
  11. Ullal A, Roberts M, Bulmer JN, Mathers ME, Wadehra V. The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia. Cytopathology 2009 Dec;20(6):359-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18557985.
  12. Jordan J, Arbyn M, Martin-Hirsch P, Schenck U, Baldauf JJ, Da Silva D, et al. European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1. Cytopathology 2008 Dec;19(6):342-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19040546.
  13. Bentley J, Society of Canadian ColposcopistsHealth professionals, usually gynaecologists, trained to perform colposcopy.. Colposcopic management of abnormal cervical cytology and histology. J Obstet Gynaecol Can 2012 Dec;34(12):1188-206 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23231803.
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