宫颈腺癌检测——新的筛查机遇?

目前还不清楚宫颈腺癌发病率增加的原因。但有几项研究显示，宫颈腺癌正在受到越来越多的关注，因为腺疾病一般要到很严重的阶段才能检测到。诊断时，腺癌倾向于体积较大，这样的病变局部复发几率较高。1 一项针对高危病人的研究表明，在诊断为不典型腺细胞(AGC)后一年内，有87.3%的病人被查出患有癌前病变或宫颈癌。2另外，已经有报告称，腺癌比包括鳞癌在内的其他宫颈癌的死亡率更高。3检测腺病变的难度与它们的进展阶段有关。癌前病变通常无症状，而且传统的巴氏涂片检测腺疾病的能力要弱于检测鳞状细胞癌的能力。4腺癌通常发生于宫颈管腺体，比外宫颈的鳞状细胞癌更难发现，为临床检查带来困难。幸运的是，新柏氏液基细胞学系统已经通过FDA新的认证标签：参考已发表的多个同类试验，ThinPrep 2000系统与传统巴氏涂片相比，提高了检测腺细胞病变的能力。5, 6, 7, 8, 9, 10 这种细胞学方法带来的更高的预测值对临床来说至关重要，因为多数结果为AGC的女性将比显示宫颈其他部位异常的女性患鳞状上皮内高度病变、腺癌、原位腺癌或浸润癌的可能性更大。11, 12, 13

由于AGC并发其他病变的可能性极大，因此通常建议对这些病人采用更积极的随诊方式。如果初始评估结果(阴道镜与锥切)正常，随诊中应当连续每4到6个月做细胞学检查，共进行四次。11, 12, 13

尽管宫颈腺癌发生率增加的原因尚未明确，但据估计，可能的风险因素包括子宫疾病史、使用某些激素、性交史与HPV感染。当在AGC病例中发现HPV时，大多数是HPV 18或16型。然而，与鳞状病变不同，HPV 18型比16型在腺癌中更常见。2, 13, 14, 15, 16 值得注意的是，由于HPV对腺疾病的影响仍未被完全阐明，因此不推荐采用HPV DNA测试用于AGC随诊。正如Digene® HPV使用说明中描述的“HPV在细胞学AGUS结果中的作用不明。”17 最近的研究中显示，细胞学结果为腺病变的病例有57%可能是HPV阴性的。14 随着宫颈腺癌发生率的升高，在日常宫颈筛查中使用液基细胞学测试，并对AGC结果采用更积极的随诊措施，有希望对这种具有挑战性诊断的早期检测与管理起关键作用。

参考：

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.