Diagnosis and management of cervical cancer

Sources and selection criteria

We searched the literature to identify all relevant articles published from 1966 to March 2007 (PubMed and Cochrane database) using a combination of the terms “cervical cancer”, “diagnosis”, and “management”. Variables of interest were cervical cancer, surgery, chemotherapy, radiotherapy, chemoradiotherapy, complications of treatment, recurrence, and follow-up. Much of the clinical management discussed in this review was based on meta-analyses, systematic reviews, and phase III randomised controlled trials (RCTs).

What causes cervical cancer?

Infection with high risk types of human papillomavirus is the main cause of cervical cancer.6 This has obvious implications for primary prevention (vaccination) and secondary prevention (screening) of this disease.

How does cervical cancer spread and what are the symptoms?

Cervical cancer usually originates in the transformation zone of the cervix, and spreads to regional lymph nodes. Parametrial invasion is also common. Clinical presentation depends mainly on the location and extent of disease. Precancerous changes or very early stage disease are usually asymptomatic and are detected on a cervical smear. Symptoms usually appear when the tumour causes spontaneous or contact bleeding, or pain if lymph nodes are involved. Other symptoms include serosanguineous foul smelling vaginal discharge or backache.

How is cervical cancer diagnosed?

When a lesion is visible with the naked eye, conisation is contraindicated, and a cervical biopsy will usually provide the diagnosis. Conisation is indicated when frank invasion cannot be ruled out by a colposcopically directed biopsy, or when colposcopy is unsatisfactory and the results of a smear test show a high grade lesion.

Pathology

Squamous cell carcinoma accounts for about two thirds of all cervical cancers. Adenocarcinoma has many histological variations and is found in 15-25% of cases. Unusual histological variants include clear cell carcinoma, neuroendocrine carcinoma, and adenosquamous carcinoma. Tumour grade (well differentiated, moderately differentiated, and poorly differentiated), depth and width of invasion, and presence (or absence) of invasion of lymphovascular space are prognostic factors that should be adequately assessed.

Cervical cancer is a clinically staged disease

The International Federation of Gynaecology and Obstetrics (FIGO) staging system is the most commonly used (table⇑).7 It takes into account the results of the physical examination, colposcopy, histopathology (cervical biopsy or conisation), radiography (for example, chest radiography, intravenous pyelography, and barium enema), and endoscopy (for example, cystoscopy or sigmoidoscopy). Suspected invasion of the bladder or the rectum should be confirmed by biopsy.

What is the value of imaging techniques?

Computed tomography or magnetic resonance imaging is often used to define lymph nodes status and to assess the extent of local disease.8 Because they rely on size and morphological criteria to recognise lymph node metastases, it is difficult to identify normal sized nodal metastases using these methods. A recent prospective study with histopathological results as a reference found that combined positron emission tomography and computed tomography may be useful for detecting smaller nodal metastases.9

What is the value of surgical staging?

Surgical staging includes pelvic lymphadenectomy and para-aortic lymphadenectomy. Many investigators have reported excellent results after surgical staging, but the only RCT found no survival advantage of surgical staging over clinical staging.10 A non-randomised comparison of extraperitoneal and transperitoneal surgical staging found that both techniques had similar accuracy and surgical complications, but a lower rate of enteric complications after irradiation was noted with the extraperitoneal approach.11 Laparoscopic extraperitoneal approaches may take advantage of both laparoscopy and retroperitoneal dissection.12 Compared with FIGO clinical staging, surgical staging improved the accuracy of diagnosis in 24% of stage IB tumours, 52% of stage II tumours, and 45% of stage IIIB tumours.13

Is clinical staging still the gold standard?

Evidence now shows that computed tomography, magnetic resonance imaging, positron emission tomography, and surgical staging are better than clinical staging for identifying the true extent of the disease. However, none of these methods has been incorporated into the FIGO staging system yet. The main reason is that cervical cancer is most prevalent in developing countries, and staging methods should be universally available, standardised, and comparable around the world. There is also still a lack of consensus about the best imaging modality and the value of surgical staging. Future FIGO staging systems may consider incorporating some of these investigations into the classification.14

Managing early stage disease

FIGO stage IA2, IB1, and IIA (figure)⇓

Radical hysterectomy is the treatment of choice for young healthy patients because it preserves ovarian function. Radiotherapy is thought to be equally effective for patients with early stage disease. An RCT comparing primary surgery with primary radiotherapy in 347 patients with stage IB-IIA cervical cancer showed that disease free and overall survival for the two groups were the same.2

Algorithm for the treatment of early stage cervical cancer

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Managing advanced stage disease

Follow-up

The aim of follow-up is to detect relapse at a stage where salvage treatment has the best chance of being effective and to monitor and treat treatment related toxicity. Most recurrences occur in the first two years after primary treatment. Physical examination includes rectovaginal examination, nodal assessment (especially supraclavicular), and cervical smears. Examinations should be performed every three to four months in the first three years.24 Thereafter, they should be performed every six months and after five years annually. Pain, vaginal bleeding, and gastrointestinal or genitourinary dysfunction must be investigated.

Treating recurrent disease

Recurrent cervical cancer is almost always incurable and less than 5% of patients who develop recurrence are alive at five years. Patients who develop pelvic recurrence after radical hysterectomy may be salvaged with chemoradiotherapy if they have not previously been irradiated.25 Central pelvic recurrences after radiation or chemoradiotherapy may undergo curative surgery with pelvic exenteration in the absence of metastatic disease.25

Conclusions

Over the past few years, in most industrialised countries women with cervical cancer have benefited from improved imaging techniques, better treatments (including chemoradiotherapy), and more conservative surgical approaches. In low resource settings—where facilities for radiology, chemoradiotherapy, and supportive care are limited or unavailable—it is important to identify which resources fill healthcare needs most effectively and to consider alternative approaches. In the near future, the best way to improve mortality and morbidity from cervical cancer will probably be to focus on primary prevention with prophylactic vaccines against human papillomavirus.