Cervical Cancer

J.A. Lacombe, G. Del Priore and J. Hillier

Introduction

Approximately 12000 women were newly diagnosed with cervical cancer in the USA in 2003.1 Although cervical cancer remains a leading killer of women worldwide, the incidence in the USA represents a significant decrease, mainly attributable to the widespread implementation of Pap test screening. The Pap smear is designed for detecting pre-invasive disease of the cervix. This allows treatment to be initiated prior to the development of cancer.2

Human papillomavirus (HPV) is a sexually transmitted virus associated with cervical dysplasia and invasive cancer. Low-risk HPV types, such as 6 and 11, are associated with cervical intraepithelial neoplasia (CIN) I and condyloma. High-risk types of HPV, such as types 16, 18, 31, 33 and 35, are observed in association with high-grade dysplasia or cervical cancer. HPV DNA can be detected in close to 100% of patients with invasive cervical cancer. Although the prevalence of HPV in some populations approaches 30-90%, only a small number of these women go on to develop cervical cancer.2

The overwhelming majority of cervical carcinomas have historically been of squamous cell histology. However, with improvement in the diagnosis and treatment of pre-invasive cervical cancer the percentage of adenocarcinomas has steadily risen from the 1970s to the present. In 1996 24% of diagnosed cervical cancer was adenocarcinoma representing a twofold rise in incidence from 1973.3 The diagnosis, treatment and prognosis of both histological subgroups appear to be similar.

Staging

Because the majority of the cases of cervical cancer worldwide are in women living in underdeveloped countries, staging systems for cervical cancer have been clinically based. Staging procedures have accordingly been geared towards technologies available within these countries.

The International Federation of Gynecology and Obstetrics (Federation Internationale Gynecologique Obstetrique or FIGO) along with the World Health Organization last revised its staging system in 1995.4 The FIGO staging (Table 2.1) system is based upon a thorough clinical examination, chest X-ray, intravenous pyelogram, cystoscopy, proctoscopy and barium enema as indicated. The physical examination should include abdominal, pelvic, rectovaginal and lymph node examinations. Examination under anaesthesia is strongly recommended because of the added benefits of muscular relaxation and inter-examiner correlation.5 If up-to-date imaging methods are available such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning, an examination under anaesthesia EUA may not be needed for treatment planning.

According to the FIGO staging guidelines, a major distinction exists between micro-invasion stage IA disease versus macroscopic stage IB disease. Micro-invasive disease is further delineated as stage IA1, with stromal invasion less than 3 mm in depth with a maximum horizontal spread of 7 mm and stage IA2, defined as stromal invasion up to 5 mm with the same horizontal spread up to 7 mm on a single histology slide. Micro-invasive cervical cancer is generally diagnosed upon cone biopsy following an abnormal Pap smear and colposcopy. Stage IA disease generally carries an extremely good prognosis. However, these distinctions are of extreme importance in the determination of which patients can be treated conservatively versus those who require more aggressive treatment.5,6

The American Joint Committee on Cancer (AJCC) has established a TNM (tumour, node, metastasis) classification system based on the same clinical staging information as FIGO. According to the AJCC, the T stages correspond to the FIGO stages. The AJCC recommends that surgical and pathologic findings be recorded as a final pathologic (TMN) disease stage, but should not change the clinical FIGO stage.

Controversy exists regarding surgical staging for cervical cancer. In 1980 the Gynecologic Oncology Group (GOG) reported a greater than 30% risk of para-aortic lymph node metastasis in patients with locally advanced cervical cancer, i.e. stages IB2-III.7 Many authors have advocated lymphadenectomy in cervical cancer for prognostic information as well as to assist in the planning of radiation fields.5,8 The advent of laparoscopy has made this procedure less morbid, thereby renewing interest in surgical staging.8 However, a consistent survival benefit has not been demonstrated.5

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