VOL. 1 JANUARY 2007

Adenocarcinoma of the Cervix -
the New Screening Opportunity
The cause of the increase in cervical adenocarcinoma is unclear, but it is of particular concern as studies have shown that glandular disease is often at a more advanced stage when detected. At diagnosis, adenocarcinomas tend to be large and bulky, and local recurrence is more common in such lesions.1 One study of high-risk patients showed that within 1 year of the initial atypical glandular cell (AGC) diagnosis, preneoplastic or neoplastic lesions were detected in 87.3% of patients.2 In addition, adenocarcinomas have been reported to have a higher fatality rate than other cervical cancers, including squamous cell lesions.3 In part, the advanced stage of these lesions is related to the difficulty associated with detecting them. Precancerous lesions are asymptomatic, and the conventional Pap smear is recognized as having a lower sensitivity for detecting glandular lesions compared with squamous cell carcinomas.4 Adenocarcinomas arise from endocervical glands which are less visible than ectocervix squamous cells making detection a challenge.

Fortunately, one of the liquid-based Pap tests, The ThinPrep® System, has FDA approved labeling, that references multiple peer-reviewed publications which report on the improved ability of the ThinPrep® 2000 System to detect glandular disease versus the conventional Pap smear.5, 6, 7, 8, 9, 10 The greater predictive value of this cytologic method is important, since a significant percentage of women with AGC will have high-grade preinvasive squamous disease, adenocarcinoma, adenocarcinoma in situ, or invasive cancers from sites other than the cervix.11, 12, 13

Because of this high likelihood that AGC is associated with significant disease, aggressive follow-up has been highly recommended for these patients. If all initial evaluations (colposcopy and cone biopsy) produce normal results, follow-up should include four consecutive Pap smears every 4 to 6 months.11, 12, 13

Although the cause of the increase in cervical adenocarcinoma is unclear, probable risk factors include history of uterine disease, certain hormone use, sexual history and HPV infection. When HPV is found in AGC cases, it is predominantly HPV 18 or 16. However, unlike squamous lesions, HPV type 18 is more commonly seen with adenocarcinomas than type 16.2, 13, 14, 15, 16 It should be noted that the role of HPV in glandular disease has not yet been elucidated and that HPV DNA testing is not included in recommendations for AGC follow-up.12 As stated in the Digene® HPV test Instructions for Use, "There is no known utility for HPV testing in Pap AGUS results."17 Recent publications have cited that up to 57% of glandular abnormalities found in Pap testing may be HPV negative.14

With the rising incidence of cervical adenocarcinoma, routine cervical screening with new liquid-based Pap tests and aggressive follow-up of AGC results will play a key role in the early detection and management of this challenging diagnosis.


References:
  1. Liu S, Semenciw R, Mao Y. Cervical cancer: the increasing incidence of adenocarcinoma and adenosquamous carcinoma in younger women. CMAJ. 2001;164:1151-1152.

  2. Chhieng DC, Gallaspy S, Yang H, et al. Women with atypical glandular cells: a long-term follow-up study in a high-risk population. Am J Clin Pathol. 2004;122:575-579.

  3. Davy ML, Dodd TJ, Luke CG, et al. Cervical cancer: effect of glandular cell type on prognosis, treatment, and survival. Obstet Gynecol. 2003;101:38-45.

  4. Medical Services Advisory Committee (MSAC). Liquid based cytology for cervical screening. Canberra, Australia: MSAC; 2002. Available at: http://www.health.gov.au/internet/msac/publishing.nsf/ Content/ref12a-1/$FILE/msacref12a.pdf. Accessed: November 6 2006.

  5. Ashfaq R, Gibbons D, Vela C, et al. ThinPrep Pap Test: Accuracy for glandular disease. Acta Cytol. 1999;43:81-85.

  6. Wang N, Emancipator SN, Rose P, et al. Histologic follow-up of atypical endocervical cells. Liquid-based, thin-layer preparation vs. conventional pap smear. Acta Cytol. 2002;46:453-457.

  7. Bai H, Sung CJ, Steinhoff MM: ThinPrep Pap Test promotes detection of glandular lesions of the endocervix. Diagn Cytopathol. 2000;23:19-22.

  8. Carpenter AB, Davey DD: ThinPrep Pap Test: Performance and biopsy follow-up in a university hospital. Cancer Cytopathology 1999;87:105-112.

  9. Guidos BJ, Selvaggi SM. Detection of endometrial adenocarcinoma with the ThinPrep Pap test. Diagn Cytopathol. 2000;23:260-265.

  10. Schorge JO, Hossein Saboorian M, Hynan L, et. al. ThinPrep detection of cervical and endometrial adenocarcinoma: A retrospective cohort study. Cancer Cytopathology 2002;96:338-343.

  11. American Society of Colposcopy and Cervical Pathology (ASCCP) Consensus Guidelines. 2002. Available at: http://www.asccp.org/pdfs/consensus/algorithms.pdf. Accessed: November 6 2006.

  12. Institute for Clinical Systems Improvement (ICSI). Management of initial abnormal Pap smear. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2005. Available at: http://www.guideline.gov/summary/ summary.aspx?doc_id=8327. Accessed: November 6 2006.

  13. Kaferle JE, Malouin JM. Evaluation and Management of the AGUS Papanicolaou Smear. Am Fam Physician. 2001;63:2239-2244.

  14. Altekruse SF, Lacey JV Jr, Brinton LA, et al. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States. Am J Obstet Gynecol. 2003;188:657-663.

  15. An HJ, Kim KR, Kim IS, et al. Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study. Mod Pathol. 2005;18:528-34.

  16. Derchain SF, Rabelo-Santos SH, Sarian LO, et al. Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears. Gynecol Oncol. 2004;95:618-623

  17. Digene Corporation. Hybrid Capture® 2 High-Risk HPV DNA Test. Updated 2004. Available at: http://www.digene.com/pdf/L2290-P.I, %20hc2%20HPV%20DNA%20Test%20US.pdf. Accessed: November 6 2006.

  18. Andersson S, Larson B, Hjerpe A, et al. Adenocarcinoma of the uterine cervix: the presence of human papillomavirus and the method of detection. Acta Obstet Gynecol Scand. 2003;82:960-965.
    19.



Pap Test Imaging
Provides Value to Both
Patients and the Lab

Pap testing and the
HPV vaccine—the beginning of the end for cervical cancer?

Abstracts in Cervical Screening
A peer commentary of the most significant articles recently published in the leading cervical health journals.

Scott A. Sullivan, MD, MSCR, FACOG

Edward J. Wilkinson, MD

Edward Charles Grendys, Jr., MD, FACOG, FACS
© 2007 Cytyc Corporation All Rights Reserved.