Imaging of cervical cancer (2024)

Abstract

Epidemiology

There are approximately half a million new cases of cervical cancer diagnosed each year worldwide, 80% in the developing nations [1, 2]. There is a worldwide fall in the incidence of cervical cancer [1]. However, there has been an apparent rise in the incidence of cervical intraepithelial neoplasia (CIN) due to effective cervical screening in the developed world. In England, the incidence of cervical cancer fell from 4467 new cases in 1985 to 2900 in 1995 and to 2424 in 2000 [3]. In terms of mortality, this is also falling by almost 7% annually in the UK. This is due to a successful cervical screening programme [4].

Clinical presentation

The peak incidence for cervical cancer is between 45 years and 50 years of age [2], although there has been a rise in the 25–34 year age group [5]. Various aetiological factors have been associated with cervical cancer. The presence of persistent human papillomavirus (HPV), smoking, age at first intercourse, multiple sexual partners, immunosuppression (such as HIV-positive women and those undergoing renal transplant) and the use of the combined oral contraceptive pill are major risk factors.

There is strong evidence that HPV is the main cause of both pre-invasive and invasive squamous cell carcinoma of the cervix [6] with HPV 16, 18, 31, 33 and 35 known to be oncogenic viruses implicated in its aetiology.

The most common clinical presentation is post-coital and/or intermenstrual bleeding. Other symptoms are foul-smelling vagin*l discharge and anaemia secondary to heavy vagin*l bleeding.

Speculum examination should be performed to visualize the cervix followed by a bimanual examination, a common finding being the presence of a hard, friable, enlarged cervix which becomes fixed as the tumour spreads. If an obvious lesion is present on the cervix, a punch biopsy should be performed [7].

The aim of the cervical screening programme is to identify women with pre-invasive cervical cancer, CIN [7]. It is important to bear in mind that the cervical smear may be negative in the presence of invasive disease [8]. However, if the cervical smear shows possible invasion, women must be referred for urgent colposcopy and be seen within 2 weeks. There is a high correlation between a smear showing features of invasion and the histological diagnosis of invasive cancer [7].

Clinical staging of cervical cancer as per the International Federation of Gynaecology and Obstetrics (FIGO), classification (Figures 1–4) [9] remains the standard approach. It should be meticulous. It is very important to determine the most appropriate form of treatment, to assess prognosis (Table 1) [10] and to evaluate and compare the results of therapy.

Clinical staging involves a clinical assessment, preferably by examination under anaesthesia performed by a gynaecological oncologist, that may or may not be supplemented by a chest radiograph (CXR), cystoscopy, intravenous urography (IVU), proctoscopy and sigmoidoscopy. Routine blood tests should include a full blood count, urea and electrolyte and liver function tests.

Histological diagnosis of stages 1a1 and 1a2 is usually made from a cone or loop cervical biopsy. When a mass is seen, histological diagnosis is obtained from a punch biopsy.

Histopathology

Squamous cell carcinomas account for 90% of cervical carcinomas. By the time they are clinically apparent, invasive squamous cell carcinomas involve the external os and are visible on speculum examination. However, some of these are within the canal and difficult to detect clinically. A squamous cell carcinoma can be exophytic, seen as a papillary or polypoid excrescence; or endophytic, infiltrating the surrounding structures. Ulceration and excavation are frequently seen. The squamous cell carcinomas are further sub-divided into three groups: large cell keratinising, large cell non-keratinising and small-cell non-keratinising [8].

Tumours arising from the glandular epithelium (adenocarcinomas) comprise 10–15% of cervical tumours. Other tumours such as endometroid, clear cell, mucinous and papillary patterns are much less common [8].

Microinvasive carcinoma refers to stage Ia FIGO; invasive carcinoma refers to pre-clinical lesion greater than 1a2 FIGO or visible clinical lesions confined to the cervix [11].

Spread or disease progression

Cervical cancer spreads predominantly by either direct invasion or by lymphatic spread. The tumour may invade into the vagin*l mucosa or into the myometrium of the lower uterine segment. If lymphatic spaces within the tumour are invaded, spread to the pelvic nodes may occur more often.

Imaging – role of MRI

Several studies correlating clinical FIGO staging as described above with surgical staging have reported FIGO staging error rates of 26–66%, depending on the stage [12]. The lymph node staging and the tumour size are now considered important prognostic factors in cervical cancer, but these are not taken into account on the FIGO clinical staging.

The availability of MRI has improved and it is becoming the imaging modality of choice for many gynaecological malignancies. This is particularly important in imaging cervical cancer. With MRI, the size of the tumour, its relationship to adjacent structures and its spread as well as the presence or absence of lymph nodes can be determined. MRI can substitute other tests such as IVU, cystogram and sigmoidoscopy and be more cost-effective [13]. We are moving towards a MR-adapted FIGO staging classification.

At our institution, MRI is obtained on almost all patients with a confirmed histological diagnosis of cervical cancer stage Ib and above to locally stage the tumour and to assess for the presence or absence of pelvic and para-aortic nodes. MRI is also performed in cases of confirmed or suspected recurrence and on occasions to assess treatment response.

MRI is performed 2–3 weeks after cervical biopsy to allow for the oedema and inflammatory changes to settle.

MRI technique

We have access to two MRI scanners, 1 T and 1.5 T Siemens scanners (Siemens, Erlangen, Germany). All the sequences are carried out with a body phase-array coil. An anterior saturation band is always used to reduce artefact from the anterior subcutaneous fat.

Patients are not being asked to fast prior to the MRI and an anti-peristaltic agent (Buscopan® if no contraindications, otherwise glucagon) is only administered if the initial sequence shows significant bowel movement artefact.

Patients are asked to aim for a half to full urinary bladder by the time of their appointment. This will help displacing the loops of bowel superiorly and therefore reduce artefact from peristalsis. A tampon is not inserted as this can significantly distort the vagin*.

Our standard pelvic sequences are axial spin echo (SE) T₁ weighted and axial turbo spin echo (TSE) T₂ weighted images of the pelvis to the level of the iliac crests, and sagittal TSE T₂ weighted from the right to the left femoral head.

High resolution axial oblique TSE T₂ weighted images, planned from the mid-sagittal plane, are obtained perpendicular to the cervical canal. If there is clinical or MRI suspicion of vagin*l involvement, high resolution axial TSE T₂ weighted images perpendicular to the vagin* are added, also planned from the midsagittal image.

To assess for the presence or absence of para-aortic nodes and hydronephrosis, axial trufi T₂ weighted images of the upper abdomen are performed. Values of these sequences as per our protocol are shown in Table 2.

The usefulness of intravenous contrast (both T₁ weighted contrast-enhanced sequences and dynamic sequences) to assess parametrial invasion has been studied [14–17]. Many of these studies have shown that an additional T₁ weighted contrast-enhanced sequence does not improve parametrial extension detection [14–16]. Dynamic MR-enhanced sequences, on the other hand, are superior to T₂ weighted images in detecting stromal and parametrial tumour extension because of the early (30–60 s) cervical tumour enhancement that helps visualization of small tumours [18, 19]; they also help predicting that tumours that enhance more would respond better to radiotherapy [17].

We do not use intravenous contrast routinely. We, as other authors [20, 21], find the high resolution axial oblique T₂ weighted images taken perpendicular to the cervical canal are very useful and sufficient to assess parametrial extension.

MRI anatomy of the cervix

The normal cervix is seen on MRI as a cylinder on the sagittal images (Figure 5a) and as a round structure on the axial oblique images (Figure 5b) where the low signal ring represents the cervical stroma and the central area of high signal represents the cervical canal with secretions. The cervical mucosa is on occasion seen as intermediate signal material inner to the low signal ring.

A cervical tumour may be seen on MRI as an area of intermediate signal on the T₂ weighted images that may or may not disrupt the low signal cervical stroma. When a mass is present, the bulk of this mass would be centred at the cervix.

In young women, cervical tumour usually originates from the squamocolumnar junction and tends to present as an exophytic mass; in older women, it originates most commonly from the endocervical canal.

Tumour staging

In stage Ib (Figure 1), with the tumour confined to the uterus, the cervix may look normal with an intact low signal cervical stroma (Figure 5a,b), or a lesion of higher signal than the stroma on T₂ weighted imaging may be seen breaching the low signal stromal ring (Figure 6). Tumour size subdivides stage Ib into stage Ib1 (4 cm and smaller) and stage Ib2 (larger than 4 cm).

According to FIGO classification, extension to the corpus of the uterus should be disregarded as the standard treatment for stage Ib tumours, with or without upper extension into uterus, is radical hysterectomy.

However, new surgical techniques, described later on in this article, are emerging for young patients who wish to preserve their fertility and therefore determining whether the tumour extends beyond internal os into uterine body is now important. The accuracy of MRI for this purpose has been studied with promising results [22].

In stage II (Figure 2), the tumour extends beyond the uterus to the upper third of the vagin*, but not to the pelvic wall or to the lower third of the vagin*. In stage IIa, there is no parametrial extension; in stage IIb, there is parametrial extension (Figure 7a,b).

Involvement of the upper third of the vagin* is one of the difficult areas for imaging. The vagin*l walls are of low signal on the T₂ weighted imaging and vagin*l involvement is considered when there is disruption of the low signal wall. If the tumour bulges into the upper vagin*, it is often difficult to ascertain whether there is or is not vagin*l wall infiltration; this is because the walls may be collapsed by the tumour. Thinner cuts with a small field of view (FOV) perpendicular to the vagin*l wall help in assessing this area. Some authors have explored the use of vagin*l contrast; this may be helpful when scanning with a low-Tesla scan or when thinner slice sections are not available [23]. However, evaluation of the vagin* is better achieved clinically.

The performance of MRI for the prediction of parametrial invasion is better than clinical FIGO classification [24]. Parametrial extension is suspected when there is interruption of the low signal cervical stroma and when there is infiltration of the adjacent parametrial fat. With an intact low signal cervical stroma, the negative predictive value for parametrial invasion is high, in the order of 97% [25].

In stage IIIa (Figure 3), the tumour extends to the lower third of vagin* (Figure 8); in stage IIIb (Figure 3) the tumour involves the pelvic wall and/or causes hydronephrosis or a non-functioning kidney (Figure 9a,b). Extension into pelvic wall means tumour is seen either abutting within 1 cm or infiltrating the muscles of the pelvic wall: obturator internus, piriform, levator ani and uterosacral ligaments.

In stage IVa (Figure 4), the tumour invades the bladder (Figure 10) or the rectum (Figure 11); in stage IVb (Figure 4) the tumour presents with distant metastases. Distant metastases from cervical carcinoma involve the abdomen, chest and bones and are mainly seen in recurrent disease.

Lymph node involvement

Determining the presence or absence of lymph node metastasis in cervical cancer is very important to assess prognosis and also to plan treatment. In all stages of cervical cancer, the presence of involved lymph nodes reduces prognosis significantly (Table 3) [26].

The prevalence of lymph node involvement varies with the stage (Table 4) [8], histological type (Table 5) [27], grade and tumour volume. A normal lymph node on MRI is seen as an oval structure, <10 mm short axis with a fatty central hilum.

The MRI features that suggest that a node may be involved with tumour are an increase in size (short axis >10 mm), a round shape and an abnormal MRI signal (intermediate on T₂ weighted images; high on short tau inversion recovery (STIR) images) with loss of the central fatty hilum replaced by central necrosis. If there is central necrosis, the positive predictive value for malignancy is 100% [28]. Sensitivity of MRI for lymph node metastases is low, however, ranging from 24% to 62% [29].

The use of an MRI lymph node specific contrast agent, ultrasmall superparamagnetic iron oxide (USPIO), is under current clinical investigation. Experience of its usefulness has been assessed in head and neck, mediastinal and breast cancer where an improvement of lymph node detection has been confirmed [30–32]. Experience in pelvic tumours is, however, small.

Given the cost and time consideration (the need to scan patients twice approximately 24 h apart) we do not anticipate incorporating the use of USPIO in our practice in the foreseeable future.

Recurrent cervical carcinoma

The most common site of recurrence from cervical carcinoma is the pelvis [33]. Distant metastases are seen mainly in recurrent disease. The liver is the most commonly involved organ [27] with metastases presenting as multiple focal masses. Metastases to the peritoneal cavity may present with ascites, subcapsular liver deposits, abdomino-pelvic soft tissue masses or omental infiltration. Involvement of para-aortic or inguinal nodes are also considered metastatic disease.

In the thorax, metastases present as multiple pulmonary nodules or mediastinal lymphadenopathy. The bones most commonly affected are lumbar spine and pelvis, usually by extension from adjacent lymph nodes [27].

Imaging – role of CT

CT is less accurate for the staging of cervical cancer, as suggested by many studies [34], but it is as good as MRI for the assessment of pelvic and para-aortic nodes and of liver metastases [21].

We prefer to use CT when metastases or recurrence are suspected as chest, abdomen and pelvis can all be examined in the same setting in a much shorter time than with MRI.

Imaging – role of PET

Positron emission tomography (PET) is a functional imaging method that uses a radioisotope that accumulates in abnormal tissue, 18-fluoro-deoxy-glucose (FDG), a glucose analogue taken up and retained by cells with an active glucose metabolism, such as malignant cells.

According to Havrilesky et al [29], for the detection of retroperitoneal nodal metastases in newly diagnosed cervical cancer and for the diagnosis of recurrent disease in cervical cancer, there is good evidence that PET is more sensitive that CT and MRI.

In our practice, the main considerations for referral for FDG-PET are: suspected recurrence with abnormal soft tissue in pelvic or retroperitoneum seen on MRI and not amenable for biopsy or in cases prior to pelvic exenteration to exclude pelvic or retroperitoneal nodal disease.

Imaging – role of ultrasound

The cervix cannot be assessed with ultrasound. On occasion, however, a large cervical tumour may be identified (Figure 12a,b). A normal ultrasound does not exclude a cervical tumour.

Treatment

The management of cervical cancer is based on treating both the primary tumour and the potential sites of metastases. The options are surgery, radiotherapy, chemotherapy or a combination of two or more of the above.

Discussion of these options should be undertaken within a multidisciplinary approach in a meeting with input from gynaecological oncologists, medical and clinical oncologists, histopathologists, radiologists and specialized oncologist nurses.

Factors affecting the management are: stage of the disease, age of the woman, her general condition and her past medical history.

The treatment based on FIGO staging is as follows:

With stage Ia1 cervical cancer, the risk of lymph node spread is less than 1% (Table 4). The diagnosis is usually made on cone biopsy of the cervix or following large loop excision of the transformation zone (LLETZ). If the excision margins are clear of the disease then no further treatment is needed. If margins are involved, a further LLETZ may be performed or the woman is offered a simple hysterectomy [11].

There is little evidence for the optimal management of stage Ia2 cervical cancer. Modified radical hysterectomy and pelvic lymph node dissection is traditionally the treatment of choice, but this leads to over-treatment of the woman. If the woman wishes to preserve her fertility then a cervical cone biopsy with extraperitoneal or laparoscopic pelvic lymphadenectomy may be performed [35].

Stage Ib1 cervical disease is the ideal stage for radical hysterectomy and pelvic lymphadenectomy.

Stage IIa is also treated surgically in a similar manner. For these women both surgery and primary radiotherapy have a similar cure rate. However, surgery is preferable in younger women as it has advantages of possible ovarian conservation and preservation of sexual function [36].

In stage IIb–IVa, a combination of radical external beam radiotherapy and concurrent chemotherapy (cisplatin) plus brachytherapy is the mainstay of treatment for advanced disease [37].

In stage IVb, where there is distant disease, treatment is palliative with multidisciplinary involvement: palliative care team, gynaecological surgeons, oncologists and nurse specialists. The aim is to achieve optimum pain control; palliative doses of radiotherapy may be used to if there is heavy vagin*l bleeding [11].

New surgical advances

Radical trachelectomy

This procedure involves removing the cervix, parametrium and the cuff of the vagin*, preserving the body of the uterus and future fertility. The procedure is combined with either extraperitoneal or laparoscopic pelvic lymphadenectomy.

It is only appropriate for selected women with early-stage cervical cancer (stage Ib or less) without vascular space invasion and low-volume disease (confined to the cervix). Other advantages are reduced blood loss and blood transfusion rate, and a shorter hospital stay as compared with radical hysterectomy [11].

Sentinel lymph node

The sentinel lymph node is the first node that drains the primary tumour. It will reflect the pathological status of the remaining lymph nodes in the lymphatic basin [38]. The sentinel lymph node identification procedure limits the extent of surgical lymph node dissection, helping to reduce operative mortality and morbidity [39].

Conclusions

Cervical cancer is one of the most important gynaecological malignancies whose prognosis and treatment are highly dependent on the stage of the disease at presentation.

At our institution, MRI is becoming more widely available and is used routinely to further stage histologically confirmed cervical tumours greater than Ib.

We perform three sequences to image the entire pelvis (axial T₁, axial T₂ and sagittal T₂), one sequence to assess the extension of the cervical tumour (high resolution axial T₂ perpendicular to cervical canal) and one to assess the upper abdomen for para-aortic nodes (axial heavily T₂ weighted), which would take approximately 30 min. An extra sequence may be needed to assess for vagin*l involvement (high resolution axial T₂ perpendicular to vagin*l canal). We do not administer intravenous contrast or vagin*l contrast routinely and the use of an anti-peristaltic agent is restricted to cases when initial sequence shows significant artefact from bowel movement.

Relevant papers published in the literature that support our technique are provided in this article.

MRI is useful for assessing the local extent of the cervical tumour and to identify abnormally enlarged nodes; but to ascertain whether these nodes are malignant or not, PET or PET-CT is more appropriate. Other imaging modalities, such as CT, assist in cases of suspected recurrence to assess for the presence of nodal disease and of metastatic disease. Ultrasound is of no value to exclude cervical disease although large tumours can be identified.

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