The cervical epithelium undergoes changes throughout the menstrual cycle and is readily accessible for examination. The epithelium covering the ectocervix is stratified and identical to that of the vagina (Fig. 37.1). It is separated from the underlying stroma by an apparent basement membrane. Superior to this is a layer of basal cells from which the other cell layers differentiate. Above the basal layer are five or six layers of parabasal cells. Above these are intermediate and superficial cell layers. The intermediate cell layer consists of large cells, each with reticulated nuclei and vacuoles of glycogen in the cytoplasm. The superficial cell layer varies in thickness, depending on the oestradiol : progesterone ratio. The superficial cells are flattened and have small nuclei, the cytoplasm containing glycogen (Fig. 37.2). A small amount of keratin is produced in some of the cells, which becomes ‘cornified’. During the reproductive years the superficial cells are constantly shed or exfoliated into the vagina, and differentiation of cells from the basal layer also proceeds constantly.

Fig. 37.1 Normal squamous epithelium covering the vaginal portion of the cervix.

Fig. 37.2 Normal exfoliated cervical cells.

The characteristics of the superficial cells can be studied by taking a smear from the cervix and staining it with Papanicolaou’s stain. In some women the nuclei become abnormally shaped or dyskaryotic, which may indicate a precancerous change; this can be detected by cervical smears.

Epidemiology of cervical cancer

Cervical cancer occurs almost exclusively in women who are or have been sexually active. There is strong molecular biological and epidemiological evidence that the predominant cause of cervical cancer is sexually transmitted human papilloma virus (HPV). There are four HPV types that are considered to be high risk (16, 18, 45 and 56), a further 11 types that are intermediate risk (31, 33, 35, 39, 51, 52, 55, 58, 59, 66 and 68) and eight that are low risk (6, 11, 26, 42, 44, 54, 70 and 73) By the age of 35, 60% of sexually active women have acquired HPV infection of the genital tract (including the vulva). This proportion is higher if the woman or her partner has had several sexual partners. In most cases the infection is symptomless and disappears within a few months (see p. 258).

Possible cofactors in cervical carcinogenesis include cigarette smoking, immunosuppression, hormonal factors and vitamin deficiencies. Prophylactic vaccination is now available either as a bivalent against the high risk HPV 16 and 18 or as the quadravalent HPV 16, 18, and the lower risk 6 and 11. A number of countries offer the vaccination from age 12–13 up to 27 years; consideration is also being given to offering the vaccine to young men before they become sexually active.

Cervical exfoliative cytology

The development of cervical carcinoma is preceded by the appearance of abnormal (dyskaryotic) cervical cells. These can be detected by microscopically examining an exfoliative cervical smear, stained using the Papanicolaou stain (the Pap test). As this is a screening test false negatives may occur, estimated at 5–15%. The proportion of false-negative smears will be reduced if strict criteria are adopted for taking and for examining the smear.

A further refinement is liquid-based cytology that involves taking cervical cells with a Cervex sampler brush and rinsing the brush into a vial of fixative. The cells are not obscured by blood or mucus and are all fixed properly. In the laboratory, a monolayer of cells is made which is easier to interpret. If the result is inconclusive, the remaining cells in the vial can be used to make a hybrid capture test, which will detect the presence of oncogenic HPV. This methodology reduces the unsatisfactory/inconclusive smear rate by 80% and has been shown to be cost-effective. A further advantage of this test is that it is likely to reduce the number of colposcopies that gynaecologists make when an inconclusive Pap smear abnormality is found. The technique has the potential to be used for the detection of other sexually transmitted diseases, such as chlamydia and gonorrhoea.

The recommended smear regimen is summarised in Box 37.1. In women aged 30 and over, the doctor or nurse taking the smear should also examine the woman’s breasts, teach her breast self-examination, and after the age of 40 measure her blood pressure.

Technique for taking a cervical smear

A tray is provided on which a bivalve vaginal speculum, some slides, a spray-on fixative plastic, a modified Ayre spatula and an endocervical brush are placed. Before performing a vaginal examination, the warmed speculum is inserted to expose the cervix. The cytobrush is inserted into the cervical canal and rotated. The sample is smeared on to the slide. The ectocervix is sampled with the Ayre spatula or Cervex brush by rotating it twice through 360° and the sample is smeared on to a slide (Fig. 37.3). If liquid-based cytology is being used the brush is placed in the liquid medium.

Fig. 37.3 Methods of obtaining cells from the cervix for cytological examination, using (1) a special wooden spatula, (2) an Ayre spatula, and (3) a Cervex sampler.

The smears are sent to a reliable, quality assured cytological laboratory for examination.

REPORTING ON SMEARS

Cytologists have agreed that nuclear abnormalities should form the basis of a cytological diagnosis. They have agreed to report smears as follows:

• Unsatisfactory. A diagnosis cannot be made because there are too few cells, there are no endocervical cells, or the slide has been processed incorrectly. The smear should be repeated 4 weeks later.

• Inflammatory or inconclusive. The nuclei are distorted by the effects of vaginal infections, such as trichomoniasis and gardnerella. The referring doctor is asked to treat the infection appropriately and then to repeat the smear.

• Normal. Repeat the smear in 1–2 years.

• Mild dyskaryosis (predictive of CIN 1). The slide may show HPV infection with no dyskaryosis, HPV infection and dyskaryosis, or dyskaryosis without HPV infection.

• Moderate dyskaryosis (predictive of CIN 2).

• Severe dyskaryosis (predictive of CIN 3) (Fig. 37.4).

Fig. 37.4 Exfoliated cervical cells showing severe dyskaryosis.

New cervical screening techniques

Meta-analysis of conventional screening found a sensitivity of 58%, a specificity of 69% and a false-negative rate of 20%. This has led to the exploration of other technologies to improve diagnostic accuracy. In the ThinPrep method, the sample is placed into a 20 mL vial of buffered alcohol, which is then prepared for automated image analysis. A study by Duke University and the American Association of Obstetrics and Gynaecology reported that this technique was cost-effective and would reduce cancer cases, deaths and serious interventions, including hysterectomy, by 57% if screening was performed every 2 years.

Detection of HPV in women:

• With negative smears carries an increased risk of developing CIN

• With low-grade abnormalities carries an increased risk of progression to a high-grade abnormality.

HPV-negative women should have repeat cervical cytology at recommended intervals. HPV-positive women should be offered colposcopic evaluation.

Telling the patient

The result of the smear should be reported to the woman by phone or by letter. This applies to all smears, not just abnormal ones. If an abnormal smear is reported, the need to counsel and explain is imperative.

To many women, the finding of a dyskaryotic smear suggests the presence of cancer. If HPV is found, many women question their own and their partner’s previous sexual behaviour. Either finding can lead to guilt, misery and anxiety. Doctors should be aware of this and should talk with the woman, explaining the meaning of the result and that HPV is not always sexually transmitted. The woman should also be told, in clear non-jargon language, what procedures may be needed. In one reported study, the term ‘precancer’ was perceived as threatening and the authors suggested that a better term would be ‘early warning cells’.

Management of abnormal cervical smears

Approaches to the management of abnormal cervical smears are summarized in Table 37.1.

Table 37.1 Management of an abnormal Pap smear

Colposcopy

Dyskaryosis is a cytological diagnosis and observer error is not uncommon. For this reason, a colposcope is often used to verify abnormal findings. A colposcope is a system of lenses that magnifies the cervix 5–20 times and enables a trained observer to translate changes in colour tone, opacity, surface configuration, vascular pattern and intercapillary distance into a diagnosis (Figs 37.5–37.8).

Fig. 37.5 Normal cervix. Opening the bivalve speculum exposes the endocervical canal, allowing examination of the full transformation zone.

Fig. 37.6 CIN 1. The abnormal epithelium is visible on both the anterior and posterior margins of the cervix, having turned white after the application of acetic acid.

Fig. 37.7 The appearance of the cervix following diathermic ablation of the dysplastic epithelium. The abnormal transformation zone has been replaced by mature squamous epithelium.

Fig. 37.8 Invasive cancer of the cervix. The cervix bleeds readily on contact.

Abnormal epithelium is white after the application of aqueous acetic acid solution (acido-white epithelium), white keratotic patches may be seen (Fig. 37.6), and the blood vessels may appear as punctate dots or as a mosaic arrangement. Bizarre branching vessels usually denote invasive cancer. A trained observer can differentiate between the minor and major cervical precancer lesions and carcinoma with a reasonable degree of accuracy. The predicted diagnosis is confirmed by punch biopsies, which are examined histologically.

Histology

Mild dysplasia is characterized by nuclear abnormalities in the basal third of the epithelium; the upper layers are not affected. In moderate dysplasia some dyskaryotic nuclei are found in the upper layers of the epithelium, and abnormal nuclei are more common (Fig. 37.9). In severe dysplasia the abnormal nuclei occupy all the epithelial layers and there is a high nuclear : cytoplasmic ratio (Fig. 37.10). Severe dysplasia may be difficult to differentiate from carcinoma in situ. In carcinoma in situ there is no differentiation as the surface layers are reached; the nuclei vary in size and stain deeply, the cells are crowded and the cytoplasm is scanty (Fig. 37.11).

Fig. 37.9 Dysplasia (moderate) (CIN 2).

Fig. 37.10 Dysplasia (severe) (CIN 3).

Fig. 37.11 Cervical biopsy from the patient whose cervical smear is shown in Fig. 37.4. Carcinoma in situ was found. (A) (× 40). There appears to be invasion of the tissues, but in reality the cells have only crept into endocervical crypts. (B) (× 160). The lack of stratification and pleomorphism of the cells is seen at higher magnification.

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN)

In some cases there is uncertainty about the exact histological diagnosis and whether the identified lesion will regress, persist or progress. This has led to a classification that includes all grades of dysplasia, the CIN classification (Table 37.2).

Table 37.2 CIN classification

GRADE	DESCRIPTION
Grade 1	Mild dysplasia
Grade 2	Moderate dysplasia
Grade 3	Severe dysplasia/Carcinoma in situ

Natural history of CIN

The current belief about the natural history of CIN is shown in Figure 37.12.

Fig. 37.12 The ‘lifecycle’ of unstable cervical epithelium.

Management of CIN

The management of CIN depends on the age of the woman, her desire to reproduce, and on the location and extent of the lesion. Current recommendations for treatment are described below.

CIN grade 1

There is a lack of agreement about management if colposcopically controlled biopsy shows mild dysplasia (CIN 1). Some gynaecologists recommend careful observation, as the majority of lesions will resolve spontaneously, but increasingly specialists are recommending that the lesion be obliterated using one of the methods outlined in the management of CIN 2 and 3.

CIN grades 2 and 3

These major-grade lesions require either local destructive treatment or excision of the suspect area. Local destructive treatment includes laser, cryosurgery and electrocoagulation diathermy. The selection of patients is important, the whole lesion must be visible and invasive cancer must have been excluded. All treatments can be given under local anaesthesia or general anaesthesia depending on the patient’s and the gynaecologist’s preference. Following ablation the smear and colposcopy returns to normal in over 90% of women.

Each of these treatments may be followed by a bloodstained or clear discharge for 1–3 weeks. About 5% of women have vaginal bleeding, and the patient may complain of pain or severe discomfort. Sexual intercourse and the use of tampons should be avoided for 4 weeks to allow complete healing. The treatments do not affect the woman’s fertility or alter the course of a subsequent pregnancy.

An alternative method of treatment is large loop excision of the transformation zone (LLETZ), with ball cautery to the exposed area of the cervix if needed to achieve haemostasis. The advantage is that the tissue can be examined histologically to exclude invasive cancer, particularly if the suspect areas extend up the cervical canal and their upper limit cannot be identified by colposcopic inspection. The whole transformation zone and some of the cervical canal area is excised. If the procedure is performed by an experienced gynaecologist there appears to be no adverse effect on the duration of a subsequent pregnancy.

If the upper limit of abnormality cannot be adequately visualized then a cone biopsy is indicated. Knife conization, usually with suturing to repair the cervix, is associated with a 10% chance of postoperative haemorrhage. If the woman becomes pregnant, there is an increased risk of miscarriage in the second quarter of pregnancy and she may give birth to a preterm baby, as a result of an incompetent cervix. The risk increases with the size of the cone excised. Ultrasound surveillance of the cervical length during the second trimester will help identify those at risk of premature delivery. Conversely, scarring can cause stenosis of the cervical canal, which can result in cryptomenorrhoea or can prevent the cervix dilating during labour, necessitating delivery by caesarean section.

Depending on age, the presence of other gynaecological conditions (for example, fibroids or menorrhagia) and personal preferences, some women with CIN 3 may choose hysterectomy.

As mentioned, follow-up is essential. The woman should be reviewed 6 and 12 months after treatment, when a cervical smear is taken and a colposcopic examination performed. If the cytology is negative and the colposcopy normal, annual smears are made from then on. Following hysterectomy for CIN, 6-monthly smears should be made for the first year and every 2 years thereafter, as abnormal cells may be found in the upper vagina, signifying vaginal CIN.

Psychological effects of CIN on women

Many women diagnosed as having CIN become depressed and upset, particularly if a health professional implies that they have been sexually promiscuous.

The woman may be concerned that her partner has been or is continuing to be unfaithful. Her attitude to sexual intercourse may change, and she may want to avoid sex.

The anxieties and uncertainty should be resolved, as far as possible, by giving the woman a full explanation of CIN and giving her the opportunity to ask questions. She may also need continued psychological support.

CERVICAL CARCINOMA

Carcinoma of the uterine cervix is the second most common gynaecological cancer (after breast cancer). The annual risk for women over the age of 35 is 16 per 100 000, but is much greater in developing countries. The peak incidence is between the ages of 45 and 55, the mean age being 51.4 years, with a recent trend towards a younger age. Cervical cancer usually grows outwards, becoming a fungating mass; occasionally it grows inwards, enlarging the cervix. More than 85% of cervical cancers are squamous cell carcinomas; the remainder are adenocarcinomas, which arise from the cells lining the cervical canal or its clefts. With time, the cancer spreads either by direct extension upwards to involve the uterine cavity, downwards to involve the vagina, or via the lymphatic drainage to the external iliac lymph nodes (47% of cases); the obturator lymph node (20%); the hypogastric nodes (7%); or the paracervical nodes (2%).

Clinical staging is not able to detect spread to the liver and lymph nodes. Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are used. CT can detect lymph node metastases, plus liver, urinary tract and bone involvement. MRI has a role in detecting parametrial spread and is particularly useful in evaluating pregnant women, as it avoids exposing the fetus to radiation. The place of positron emission tomography (PET) is still being assessed but it has the potential to accurately determine the extent of spread from the cervix and lymph node involvement.

Accurate staging of the disease is critical to determine the optimal mode of treatment, and the International Federation of Obstetrics and Gynaecology (FIGO) classification is summarized in Table 37.3. The higher the stage on the initial examination, the greater the chance of lymph node involvement and the poorer the prognosis (Table 37.4). In early-stage disease (stages 1B and 2A, see later) lymph node metastases are present in 25–30% of cases.

Table 37.3 International Federation of Obstetrics and Gynaecology (FIGO) classification for staging of carcinoma of uterine cervix

STAGE	DESCRIPTION
Stage 0	Cervical intraepithelial neoplasia 3 (CIN 3), Carcinoma in situ
Stage 1	The carcinoma is confined to the cervix 1A Invasion can only be diagnosed by microscopy with maximum depth ≤5.0 mm and horizontal spread of ≤7.0 mm 1B Clinically visible

Stage 2 The carcinoma invades beyond the uterus but does not reach pelvic wall or lower third of the vagina

2A No obvious parametrial involvement

2B Obvious parametrial involvement

Stage 3 The carcinoma has reached the wall of the pelvis and/or the lower third of the vagina

3A Reached lower third of the vagina

3B Extension to pelvic wall or hydronephrosis or non-functioning kidney

Stage 4 The carcinoma has spread beyond the true pelvis or has invaded the bladder or rectum

4A Spread to adjacent organs

4B Spread to distant organs

Table 37.4 Lymph node involvement and 5-year survival rates of cervical carcinoma related to stage of the disease

STAGE	LYMPH NODE INVOLVEMENT	5-YEAR SURVIVAL (%)
0	0	100
1A	0.5	95
1B	15	80
2A	25	66
2B	35	64
3	55	35
4	>65	14

Diagnosis

In its earliest stage an abnormal smear is the only way to detect cervical cancer, as symptoms tend to occur only with established invasive disease. Irregular bleeding per vaginam, particularly after sexual intercourse, or a pink vaginal discharge after urination, demands investigation by vaginal examination using a speculum and a cervical smear. Diagnosis is confirmed by a cervical biopsy, if necessary under colposcopic direction or, if gross evidence of cervical cancer is detected, by biopsy and endocervical curettage.

Treatment

The best results of treatment for cervical cancer are obtained in oncological units staffed by gynaecological and radiological oncologists. The treatment of microinvasive (stage lA) cancer depends on whether or not the woman wants to retain her uterus. In this circumstance a cone biopsy with clear margins is adequate treatment. Otherwise it can be treated by simple total hysterectomy.

Stage 1B and early 2A cancer is usually treated by radical hysterectomy followed by radiotherapy. Radical hysterectomy includes removal of the parametrium and pelvic lymphadenectomy, and radiotherapy includes a combination of external beam and intracavity radiation. In younger women the ovaries can be preserved and relocated out of the potential radiotherapy field. More advanced cervical carcinoma is treated by radiotherapy, although in some centres chemotherapy is being tried.

Bladder dysfunction, lymphoedema and sexual dysfunction are complications of treatment, especially of radiotherapy.

Chemotherapy has been used in both early stage (1B) and advanced disease. This improves the 2-year survival rate from 79 to 89% and 63 to 75%, respectively.

ENDOMETRIAL CARCINOMA

Endometrial carcinoma is a disease of women in their middle years, the peak incidence occurring in the 55–65-year age group. Women whose menopause is delayed beyond the age of 55, who are relatively infertile, and overweight or hypertensive are more likely than other women to develop endometrial cancer. This profile suggests that unopposed oestrogen may play a role in the development of the cancer. As discussed on page 297, unopposed oestrogen may lead to endometrial hyperplasia (Fig. 37.13). Endometrial hyperplasia has several pathological appearances, and if the pathology shows complex hyperplasia with atypia 17–43% of women will develop endometrial cancer, unless they are treated.

Fig. 37.13 Transvaginal ultrasound showing endometrial hyperplasia.

The tumour may originate in any part of the endometrium, and grows slowly, tending to spread over a part of the endometrium before invading the myometrium. If the growth starts in the lower part of the uterus, the fungating mass may block the cervix and fluid or pus may collect in the uterus (pyometra). Various histological patterns of adenocarcinoma are found on the histological examination of an endometrial biopsy or curettage. The more undifferentiated the endometrial cells, the worse the prognosis. The cancer is staged using the FIGO classification (Table 37.5).

Table 37.5 Surgical–pathological staging of endometrial carcinoma (FIGO, 1989)

STAGE	DESCRIPTION
IA	Tumour limited to endometrium
IB	Invasion to <1/2 myometrium
IC	Invasion to >1/2 myometrium
IIA	Endocervical glandular involvement only
IIB	Cervical stromal invasion
IIIA	Tumour invades serosa and/or adnexae and/or positive peritoneal cytology
IIIB	Vaginal metastases
IIIC	Metastases to pelvic and/or para-aortic lymph nodes
IVA	Tumour invades bladder and/or bowel mucosa
IVB	Distant metastases including intra-abdominal and/or inguinal lymph node

Clinical features

The usual symptoms of endometrial carcinoma are a bloody vaginal discharge or irregular bleeding, which is slight in amount and recurrent. Some women have a watery vaginal discharge, but this is uncommon. Examination usually shows a normally sized uterus, unless there are associated myomata or a pyometra. Any peri- or postmenopausal woman who has symptoms of irregular bleeding per vaginam or a bloody vaginal discharge must be examined and endometrial and endocervical canal tissue sampled. Using a hysteroscope, the uterine cavity can be inspected and a biopsy taken under direct vision. An alternative is to measure the thickness of the endometrium by transvaginal ultrasonography. If the endometrium is less than 5 mm thick, endometrial cancer can be excluded. Confirmation is by hysteroscopy and biopsy or by curettage, either using a biopsy curette (this can be done as an outpatient procedure) or a formal curettage under general anaesthesia. Two biopsy curettes are commonly used (Gynescan and Pipelle). They are introduced through the cervix and rotated in the uterine cavity. The procedures are said to be relatively painless, but 60% of women experience discomfort or pain. A negative biopsy in a symptomatic woman should be followed by a formal hysteroscopy and biopsy/curettage under anaesthesia, as there is a 10% false-negative rate.

Screening for endometrial cancer

Mass screening for endometrial cancer is neither practical nor justifiable with currently available techniques. Papanicolaou smears will detect 50% of cases but is too unreliable to be used for screening asymptomatic women. Three groups are at high risk: postmenopausal women taking unopposed oestrogen therapy, women with a familial history of non-polyposis colorectal cancer, and premenopausal women with anovulatory cycles. These women should be offered regular surveillance, including transvaginal ultrasound examination. Women taking tamoxifen are only at risk if they have abnormal vaginal bleeding.

Treatment

Over 75% of cases are diagnosed when the cancer is at an early stage. Total hysterectomy and bilateral oophorectomy is the treatment of choice in these cases. As lymphatic spread is a later development, pelvic lymphadenectomy is performed only with grade 3 disease (>50% non-squamous or non-morular growth pattern), grade 2 (6–50% non-squamous or non-morular growth pattern) tumours >2 cm in diameter, adenosquamous, clear cell or papillary serous carcinomas, >50% myometrial invasion, or in those with cervical extension. The excised uterus is examined histologically, and if the myometrium has been invaded to more than half its thickness, either whole pelvis irradiation (50 Gy over 5 weeks) or hormone treatment is given. Some gynaecological surgeons arrange for intravaginal irradiation 3–4 weeks after the hysterectomy, giving 40 Gy. The objective is to prevent recurrence in the vaginal vault. Problems with this approach are that the vaginal vault may become stenosed, making intercourse uncomfortable, and that bladder or rectal symptoms may occur as a result of radiation damage.

If the patient is unfit for surgery or if the cancer is advanced, hormone treatment such as medroxyprogesterone acetate 200–400 mg orally daily may be used as an alternative.

Prognosis

The prognosis depends on the stage of the disease, the histological grade of the tumour and the age and health of the woman (Table 37.6).

Table 37.6 The recommended treatment and 5-year survival rate of endometrial cancer related to the stage of the disease

STAGE	RECOMMENDED TREATMENT	5-YEAR SURVIVAL RATE (%)
IA	Hysterectomy	90
IB	Hysterectomy	88
IC	Hysterectomy followed by vaginal vault and pelvic irradiation	80
IIA	As for carcinoma of cervix	77
II B	As for carcinoma of cervix	67
III	Hysterectomy and bilateral salpingo- oophorectomy if feasible plus radiation therapy	40
IV	Palliative surgery, radiation therapy and progestogenic therapy	10

Women who have received treatment for low-stage endometrial carcinoma and who have severe menopausal symptoms may be prescribed hormone replacement therapy with no increased development of any residual cancer.

Follow-up is recommended at 4-monthly intervals for the first 3 years, and annually thereafter. The woman is examined abdominally and vaginally, checked to detect any enlarged lymph nodes, and a chest X-ray is taken.

VULVAL DISEASE

Vulval intraepithelial neoplasia (VIN)

This condition is being increasingly diagnosed during the colposcopic investigation of women presenting with pruritus vulvae or vulval warts. The best treatment is unknown. The options are watchful expectancy or local excision of the area in high-grade VIN 3. Follow-up is important, as one-third of patients have recurrent disease.

Between 4 and 8% of women with Paget’s disease have an underlying adenocarcinoma. Treatment is by wide excision, including the underlying dermis. Because of the high rate of recurrence these women need long-term surveillance.

Carcinoma of the vulva

Vulval carcinoma accounts for 3% of genital tract cancers and affects elderly women. The growth usually starts as a lump or an ulcer on one labium majus (50% of cases) or on a labium minus (25% of cases). In some cases several areas are affected. In recent years a number of younger women have been presenting with malignant change in a vulval condyloma.

The affected woman may have complained of vulval itching for months or years, or may have had few symptoms and has only noticed the lump or the ulcer recently.

Clinical

The lesion presents as a hard nodule or an ulcer with a sloughing base and raised edges, which may be small or large depending on the duration of the disease (Fig. 37.14). If the cancer is large, lymph node involvement will have occurred in more than 50% of cases.

Fig. 37.14 Vulval carcinoma in the anterior part of the vulva.

Treatment is either simple vulvectomy with dissection of the inguinofemoral lymph nodes for stage 1 disease (tumour = 2 cm), or radical vulvectomy for stage 2 (confined to the vulva and >2 cm in diameter) with inguinal, femoral and pelvic lymphadenectomy. Wound necrosis is a troublesome complication after radical vulvectomy, and persistent leg oedema occurs in 20% of women. For women with advanced disease the treatment needs to be individualized and depends on the degree of spread, the age of the woman and her general state of health. The modalities employed include surgical excision, radiotherapy and chemotherapy.

The overall 5-year survival is 70%; for stage I 90%, stage II 75%, stage III 50%, and stage IV 15%.

CANCER OF THE OVARY FOLLOWED BY ULTRASOUND (FIG. 37.15)

Malignant ovarian tumours are rarely diagnosed early and, in consequence, carry a high mortality. About 6% of ovarian tumours are found to be malignant at surgery, the proportion increasing as a woman grows older.

Fig. 37.15 Transvaginal scan showing 12 × 9 cm malignant ovarian tumour. Note the irregularity and the solid and cystic areas.

The tumour may arise in several ways, as shown in Table 37.7.

Table 37.7 A classification of the commoner malignant ovarian tumours

Primary ovarian carcinoma accounts for about 20% of all gynaecological cancers. In more than 70% of cases the growth has spread beyond the ovaries when first detected. By this time the prospect of 5-year survival is less than 25%.

Up to 10% of ovarian epithelial cancers have a genetic origin, with several family members being affected. The strongest association is with the BRCA1 gene, located on chromosome 17, and a smaller number with the chromosome 13 BRCA2 gene. About 40% of current female family members with a BRCA1 mutation will develop ovarian cancer, and up to 87% with BRCA1 or BRCA2 mutations will develop breast cancer. Some authorities suggest a prophylactic bilateral oophorectomy when the woman has completed her family.

Clinical features

The woman, who is usually aged 50 or more, may notice that her abdomen is becoming larger (from the mass, or from ascites), or she may complain of pressure symptoms on her bladder or rectum. Abdominal discomfort and gastrointestinal symptoms may be present. She may have lost weight and have a poor appetite. In most cases the symptoms are few if any and the tumour is detected during a routine examination Germ cell malignancies can affect women under the age of 30, the most common being dysgerminoma. The FIGO staging of ovarian cancer is shown in Table 37.8.

Table 37.8 FIGO staging and 5-year survival of ovarian cancer

STAGE		5-YEAR SURVIVAL (%)
I	Growth limited to ovaries	85
II	Growth involving 1 or both ovaries with pelvic extension	60
III	Peritoneal implants outside the pelvis	30
IV	Distant metastases	10