HPV status in sentinel nodes might be a prognostic factor in cervical cancer
Introduction
The “sentinel node” is defined as the first lymph node encountered by lymphatic vessels draining a tumor. Theoretically, if the sentinel node does not show metastatic lesion, then all other nodes should also be disease-free. For patients with melanoma and breast cancer, the sentinel-node procedure is already well established and has become the standard procedure for determining nodal stage [1], [2]. However, except for vulvar cancer [3], [4], the clinical utility of sentinel-node procedure is still under evaluation for gynecologic malignancies including cervical cancer. Different from melanoma or breast cancer, the use of sentinel-node procedure in patients with cervical cancer does not offer cosmetic benefit. But considering that pelvic lymphadenectomy may be associated with excess morbidities due to vessel and nerve damage and edema of the legs and lymphocele formation, reduction in the frequency of extensive pelvic lymphadenectomy is certainly needed. Therefore, the sentinel-node procedure has emerged as an alternative to extensive pelvic lymphadenectomy in patients with cervical cancer.
Human papillomavirus (HPV) is now considered the primary etiologic agent in cervical carcinogenesis [5], [6], [7]. We use HPV test as an adjunctive method for the diagnosis of cervical cancer and HPV vaccine has become available for practical use. Although the clinical significance of HPV in cervical cells in the diagnosis is well accepted, the HPV status of lymph nodes and the relationship between cancer metastasis and HPV still remain uncertain. There have been a few studies that focused on the role of HPV in cancer metastasis [8], [9], [10]. The most important prognostic factor for cervical cancers in the patients with stages IB–IIA is pelvic lymph node metastasis [11], [12]. But the cervical cancer patients with pathologically non-metastatic lymph nodes have failed their treatments and experienced recurrence in a considerable number of cases [13]. It could be explained by the limitation of pathologic diagnosis of lymph node metastasis depending on microscopic morphology. Therefore, new prognostic factor overcoming the limitation of morphologic diagnosis could be beneficial and it could be valuable to find out the clinical significance of HPV status in sentinel lymph nodes on pathologic metastasis and recurrence of cervical cancer.
In this study, we examined whether the pathologic status of sentinel nodes in patients with cervical cancer represents metastatic disease in the lymph nodes and the sentinel-node HPV status plays a crucial role for predicting lymph node metastasis of the cancer. And we also examined whether the HPV status in sentinel nodes might have a clinical value as a prognostic factor for the recurrence of disease in cervical cancer patients.
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Patients
Fifty-seven patients affected by stages IB–IIA cervical cancer were enrolled in this study prospectively from the Department of Obstetrics and Gynecology, Kangnam St. Mary's Hospital, Catholic University of Korea, from August 2001 to July 2003, using a research protocol approved by our Institutional Review Board. All patients gave their informed consent for the study. All patients underwent sentinel-node biopsy and all sentinel nodes were submitted for frozen section examination during radical
Patient characteristics
Fifty-seven women were enrolled in this study. The mean age of the patients was 47.4 years (range; 25–74). According to the FIGO staging, the study included 29 patients of stage IB1 (50.9%), 15 patients of IB2 (26.3%) and 13 patients of IIA (22.8%). Their histopathological diagnoses were 45 (75.4%) squamous cell carcinoma, 4 (7.0%) adenosquamous carcinoma and 14 (24.6%) adenocarcinoma of the cervix.
Eleven patients (19.3%) had pelvic lymph node metastasis by histopathological examination after
Discussion
Carcinoma of the uterine cervix is a common cancer among women worldwide and is one of the most important health issues for women. Since the first study of sentinel-node biopsy in cervical cancer was published in 1999, several lymphatic mapping studies have been performed on patients with cervical cancer [14], [15], [16], [17]. The two main endpoints of the procedure are the sentinel-node identification rate and the false-negative rate. In this study, sentinel lymph node mapping achieved by the
Acknowledgments
This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A06-0079-AA1018-06N1-00010A).
References (31)
- et al.
Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes
Lancet
(1997) - et al.
Presence of oncogenic HPV DNAs in cervical carcinoma tissues and pelvic lymph nodes associated with proliferating cell nuclear antigen expression
Gynecol. Oncol.
(1996) - et al.
Interest of pelvic and paraaortic lymphadenectomy in patients with stage IB and II cervical carcinoma
Gynecol. Oncol.
(1999) - et al.
Histopathological validation of the sentinel node concept in cervical cancer
Ann. Oncol.
(2004) - et al.
Molecular quantification and mapping of lymph-node micrometastases in cervical cancer
Lancet
(2001) - et al.
The prognostic significance of HPV-16 genome status of the lymph nodes the integration status and p53 genotype in HPV-16 positive cervical cancer: a long term follow up
BJOG
(2003) - et al.
Detection and quantitation of human papillomavirus DNA in primary tumour and lymph nodes of patients with early stage cervical carcinoma
J. Clin. Virol.
(2005) - et al.
Poor clinical outcome in early stage cervical cancer with human papillomavirus-18 positive lymph nodes
Eur. J. Obstet. Gynecol. Reprod. Biol.
(2000) - et al.
Validation of accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial
Ann. Surg.
(1999) - et al.
Pitfalls in the sentinel lymph node procedure in vulvar cancer
Gynecol. Oncol.
(2004)
Prognostic significance of lymph node variables and human papillomavirus DNA in invasive vulvar carcinoma
Gynecol. Oncol.
The causal relation between human papillomavirus and cervical cancer
J. Clin. Pathol.
Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection
CMAJ
Human papillomaviruses and cervical neoplasia: a model for carcinogenesis
Int. J. Gynecol. Pathol.
The use of PCR technique in the evaluation of the frequency of HPV infection in vulvar and cervical carcinoma
Ginekol. Pol.
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