HPV status in sentinel nodes might be a prognostic factor in cervical cancer

https://doi.org/10.1016/j.ygyno.2006.12.016Get rights and content

Abstract

Objective.

Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor.

Methods.

From August 2001 to July 2003, 57 patients affected by stages IB–IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow-up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV.

Results.

Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P < 0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease.

Conclusion.

Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false-negative rate of the sentinel-node biopsy.

All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients.

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.

Section snippets

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)

  • P.P. Alvaro et al.

    Prognostic significance of lymph node variables and human papillomavirus DNA in invasive vulvar carcinoma

    Gynecol. Oncol.

    (2004)
  • F.X. Bosch et al.

    The causal relation between human papillomavirus and cervical cancer

    J. Clin. Pathol.

    (2002)
  • E.L. Franco et al.

    Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection

    CMAJ

    (2001)
  • M.H. Stoler

    Human papillomaviruses and cervical neoplasia: a model for carcinogenesis

    Int. J. Gynecol. Pathol.

    (2000)
  • J. Liss et al.

    The use of PCR technique in the evaluation of the frequency of HPV infection in vulvar and cervical carcinoma

    Ginekol. Pol.

    (1998)
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