If the patient has symptoms suggesting a gynaecological cancer, a gynaecological examination must always be carried out.
The Papanicolaou test (Pap smear), endometrial biopsy and (transvaginal or abdominal) ultrasonography are the principal investigations carried out in primary care.
Patients with any malignant tumours and precancerous lesions should be referred to specialized care.
Gynaecological cancers are encountered in all age groups. The incidence peaks in the 60-70 age group.
Some of the cancers of the female genital organs only cause a few symptoms and some progress into an invasive cancer via precursor stages.
Most cases are squamous cell carcinomas; melanoma, basal cell carcinoma and extramammary Paget's disease are also possible.
Over 80% of cases are encountered in women aged over 65 years (peak incidence at the age of 75).
Lichen sclerosus and papillomavirus (HPV) infection are predisposing factors.
Cancers arising from lichen sclerosus often occur in older women, those associated with HPV in younger women.
Treatment of precancerous lesions of the vulva associated with HPV (HSIL/VIN2-3) (most often by laser vaporisation or surgical excision) reduces the risk of progression to cancer.
Effective treatment of lichen sclerosus (with a potent topical glucocorticoid ointment) reduces the risk of cancer.
Precancerous differentiated VIN (dVIN) caused by lichen sclerosus should be treated by surgical excision.
Symptoms and diagnosis
A burning sensation, pruritus and pain in the vulva, occasionally bloody discharge or ulceration
Burning and pruritus in an elderly woman's vulva should not be treated without first examining the patient.
There is typically an exophytic tumour or hard-rimmed ulceration.
Lesions may be bilateral.
Biopsies (punch biopsy) should be taken from the lesion; the tissue sample will confirm the diagnosis.
The stage of disease should be defined by imaging in specialized care.
Treatment and follow-up
Radical tumourectomy with wide margins of healthy tissue and, depending on the location and size of the tumour, uni- or bilateral inguinal sentinel node examination and excision, as necessary.
If there are lymph node metastases, usually adjuvant external radiotherapy or chemoradiotherapy of the groin and pelvis.
If radical excision of the tumour is not possible, chemoradiotherapy is often used. Neoadjuvant chemotherapy may be considered in order to facilitate surgery.
The most common sites for recurrences are the external genitalia and groin.
The patient is monitored in specialized care for 5 years, thereafter in primary care.
Prognosis
The overall 5-year survival rate is 50%, but 70% if the tumour is confined to the vulva.
Human papillomavirus (HPV) Human Papillomavirus (HPV) Infection infection is the most important aetiological factor (98%). Infections with the HPV types 16 and 18 cause about 70% of cervical cancers.
Cancer of the cervix continues to be the most common gynaecological malignancy worldwide.
The incidence of invasive cancer is reduced by screening programmes tailored to specific age groups (HPV test or Pap smear) and management of precancerous lesions (HSIL/CIN2-3) Pap (Cervical) Smear and Endometrial Biopsy.
Sixty to seventy-five per cent of the cancers originate from the squamous epithelium. Cancers of columnar epithelium, i.e. adenocarcinomas, account for 25-40% of cases.
Risk factors: HPV infection, smoking, sexual intercourse starting at a young age, multiple sexual partners.
Symptoms and diagnosis
In asymptomatic patients, the diagnosis is based on Pap smear and HPV test.
Symptoms may include unusual bloody vaginal discharge, postcoital bleeding or unusual excessive leucorrhoea.
Squamous cell carcinoma may present as an easily bleeding mass protruding into the vagina or as an ulcer at the external orifice of the uterus.
-Adenocarcinoma occurring predominantly in the cervical canal is more difficult to diagnose with cytology and is often not clinically visible. In some cases the cervix may become enlarged and barrel-shaped.
If a cervical tumour is suspected based on clinical examination, the patient should be urgently referred to specialized care. The Pap smear test can be done in primary care but don't wait for the results.
The determination of the stage and invasiveness of the disease is based on biopsies and/or a sample taken by loop excision, as well as on radiological examinations (pelvic MRI, computerized tomography [CT] of the chest, abdomen and pelvis or positron emission tomography [PET-CT]).
Staging is based on the clinical findings and imaging findings.
Treatment
Treatment varies with the stage of the disease.
Local superficial carcinoma (invasion depth < 5 mm) is treated with simple hysterectomy. Amputation of the uterine cervix or loop excision alone can be done in selected cases if there is a desire to maintain fertility. Pelvic lymph nodes are removed in some cases.
Invasive cancer that is confined to the cervix (Stage IB1-IB2; tumour size < 4 cm) is treated with radical hysterectomy (Wertheim's operation) and pelvic lymph node dissection. Sentinel node examination is done at the beginning of the procedure. If metastases are found in lymph nodes, hysterectomy is not performed.
Large non-metastatic tumours or tumours with more extensive local spread are treated aiming for cure by chemoradiotherapy often combined with interstitial brachytherapy. If distant metastases are detected at diagnosis, cytotoxic treatment is started to slow the spread of the disease.
Follow-up
The patient is monitored in specialized care for 3-5 years, thereafter in primary care
The primary care follow-up should consist of the patient's history and both a general and gynaecological examination.
The vulvar and vaginal mucosa should be observed and any findings on palpation of the lesser pelvis noted. Lymph node areas and the abdomen should be palpated. Lower limb oedema or side difference requires attention.
History taking should include any symptoms, such as bloody discharge, urinating difficulties, problems with bowel function or cough.
Further investigations should be done as dictated by findings and symptoms. There is no evidence on the benefit of routine Pap smear tests of asymptomatic patients for detecting recurrence. Patients should be encouraged to attend mass screening.
If recurrence is suspected, further examinations should be done in specialized care.
In cancer of squamous cell origin, the patient's hormone replacement therapy (HRT) may consist of both systemic and topical oestrogen therapy Menopausal Symptoms and Hormone Therapy. If the body of the uterus is left intact, a combination of oestrogen and progestogen is used. Systemic HRT is often contraindicated in adenocarcinomas, unless otherwise instructed by specialized care. Mucosal symptoms can be treated with topical estriol creams or suppositories.
Prognosis
The 5-year survival rate is 90% if the cancer is confined to the uterus (Stage I), 65-70% if the cancer has spread to local lymph nodes and 20-30% if the cancer has metastasised to other parts of the body.
Most often encountered in women aged between 50 and 60 years
Risk factors the same as for cancer of the cervix
Ninety per cent of cases are squamous cell carcinomas; adenocarcinoma and melanoma are rare.
Mostly asymptomatic precancerous stages (vaginal HSIL/VAIN 2-3) are diagnosed with colposcopy and biopsies prompted by abnormal Pap smear test results. Eighty per cent of the lesions are located at the vaginal fornix.
Effective treatment of precancerous lesions (often laser vaporisation or surgical excision of the lesion) prevents the development of cancer. However, there is a significant risk of recurrence.
Vaginal cancer has no specific symptoms. Vaginal bleeding may occur and physical findings may include a tumour or an ulcer.
Differential diagnosis should consider the possibility of a metastatic vaginal cancer from other organs.
A biopsy is taken from the tumour for histological examination, and imaging is used to define the disease stage as for cancer of the cervix.
The treatment of local cancer may be surgical; for the rest, treatment is as for advanced cancer of the cervix (chemoradiotherapy or cytotoxic therapy).
Prolonged exposure of the uterine mucosa to oestrogen predisposes the patient to endometrial hyperplasia Benign Gynaecological Lesions and Tumours and further to adenocarcinoma. Uterine sarcoma is rare (< 5%).
Risk factors: age, obesity, diabetes, polycystic ovaries and anovulatory cycles, nulliparity, late menopause, oestrogen therapy without progestogen, anti-oestrogen therapy (tamoxifen) and Lynch syndrome Lynch Syndrome, for instance.
Combined oral contraceptives and hormonal IUDs reduce the growth of the uterine mucosa and hyperplasia as well as lower the risk of uterine cancer after more than 5 years' use.
Women diagnosed with Lynch syndrome are counselled in specialized care and prophylactic hysterectomy and ovariectomy are recommended by the age of 40-45 years Lynch Syndrome.
Symptoms
The symptom is abnormal uterine bleeding (90%). In about 15% of cases postmenopausal bleeding is caused by uterine cancer. Bleeding in women over 70 years is due to cancer in half of the cases.
The bleeding often leads to early diagnosis.
Bleeding may be scant, brownish in colour and unlike menstrual bleeding in quantity.
Premenopausal women may report bleeding between normal menstruation, spotting or prolonged menstrual bleeding.
Diagnosis
Gynaecological examination and, if possible, transvaginal ultrasonography
Endometrial biopsy is indicated if the (particularly postmenopausal) patient presents with abnormal bloody discharge Pap (Cervical) Smear and Endometrial Biopsy. A tissue sample will allow early detection of cancer. About one woman in three with atypical endometrial hyperplasia detected by biopsy already has uterine cancer.
Ultrasonography cannot replace biopsy, and a thin endometrium (< 5 mm) does not rule out cancer.
Fluid in the uterine cavity in a menopausal woman needs to be investigated as it may be an accumulation of pus (pyometra) associated with cancer.
The stage and differentiation of cancer are defined preoperatively by taking an endometrial biopsy and by performing transvaginal ultrasonography or pelvic MRI and CT of the chest, abdomen and pelvis.
Staging is based on surgical and pathological findings.
Treatment
Treatment consists of surgical removal of the uterus and ovaries (in most cases, the cancer is confined to the uterus). In most cases, laparoscopic surgery is the optimum procedure. Depending on the preoperative risk assessment, pelvic and para-aortic lymph nodes can be removed at the same time for lymph node staging and/or a sentinel node examination can be done.
Adjuvant therapy depends on the differentiation, histological subtype, molecular markers and stage of the cancer. Intravaginal radiotherapy (brachytherapy), external radiotherapy of the pelvis (and sometimes the para-aortic region) or cytotoxic therapy, or a combination of these, can be given as adjuvant therapy.
For patients in poor health and hence not eligible for surgery, hormonal treatment can be started or palliative radiotherapy can be performed.
Hormonal treatment sparing fertility may be possible for carefully selected young patients. Hysterectomy is performed after potential pregnancy.
Follow-up
The patient is monitored in at a gynaecological outpatient clinic for 3-5 years, thereafter in primary care.
Seventy-five per cent of recurrences occur within 3 years of surgery. The most common site (50%) for a recurrence is the vagina or pelvic lymph nodes.
The primary care follow-up visit should consist of taking patient's history, both a general and gynaecological examination, and supplementary examinations depending on the symptoms and as considered necessary. If recurrence is suspected, further examinations should be done in specialized care.
Systemic oestrogen treatment is mostly contraindicated after the treatment of uterine adenocarcinoma, unless otherwise instructed by specialized care. Vaginal dryness may be treated with topical oestriol creams or suppositories.
Prognosis
Three quarters of patients have Stage I disease, and 80-90% of them are alive after 5 years.
Cancers of the ovaries, Fallopian tubes and peritoneum
In addition to the actual cancer cases, there are cases of borderline ovarian cancer, i.e. tumours which may become malignant.
The clinical picture and treatment are the same regardless of the exact anatomic origin of the cancer.
The majority (90%) of cancers of this group are epithelial tumours (serous, mucinous, endometrioid or clear cell). Germ cell tumours and sex-cord stromal tumours are significantly less common.
The incidence peaks in the 60-69-year age group, but ovarian cancer is encountered in all age groups.
The lifetime risk of a woman for developing ovarian cancer is 1-2%.
Risk factors include a family history (ovarian cancer in mother/sister, inherited gene mutation [such as BRCA1, BRCA2 Hereditary Susceptibility to Cancer, Lynch syndrome Lynch Syndrome]), nulliparity, endometriosis, HRT for menopausal symptoms (> 10 years).
Protecting factors include pregnancies, breast feeding, combined oral contraceptives, ovariectomy and/or salpingectomy, sterilisation.
Women carrying the BRCA1 or BRCA2 gene mutation, for instance, are counselled in specialized care and recommended prophylactic ovariectomy and salpingectomy by the age of 35-45 years depending on the mutation Hereditary Susceptibility to Cancer.
Symptoms
Ovarian cancer has no specific symptoms. An asymptomatic tumour is often discovered as an incidental finding.
Three out of four ovarian cancers are not diagnosed until the tumour has spread to the abdominal cavity or more extensively.
Symptoms may include pain as well as disturbed bowel and bladder function. There may be dyspnoea in association with malignant pleural effusion.
There may be a palpable abdominal or pelvic mass. Abdominal distension may be a sign of the cancer spreading to the abdominal cavity and the production of ascites.
Non-specific general symptoms may occur: weight loss, low-grade fever, weakness, fatigue.
Diagnosis
Comprehensive history, clinical examination; after obtaining abnormal clinical findings, ultrasonography and tumour marker measurements..
Final diagnosis is made with a histological examination of tissue samples in specialized care.
A tumour that is multilocular and/or partly solid and/or has papillary projections warrants an urgent referral for further investigations in specialized care.
The most commonly used tumour marker for epithelial gynaecological cancers is the CA 12-5 level in the serum. It is non-specific in women of reproductive age, in particular, as the levels may also be increased by endometriosis, inflammation, menstruation, and pregnancy. Ascites of any other cause may also increase the levels.
The measurement of the tumour marker HE4 improves both the diagnosis of early stage epithelial ovarian cancer in women of reproductive age and the discrimination between malignant tumours and endometriomas. Germ cell tumours and sex-cord stromal tumours have specific biomarkers that can be determined in specialized care, as necessary.
Chest-abdomen-pelvis CT is done in specialized care to confirm the diagnosis and to assess the stage of the disease.
Differential diagnosis includes uterine tumours (usually myomas Benign Gynaecological Lesions and Tumours), urinary retention, faecal impaction, pelvic kidney, endometriosis, intestinal tumours and tumours of the urinary tract.
Treatment
The initial treatment of choicefor epithelial ovarian cancer is surgery which aims to achieve maximal cytoreduction in the abdominal cavity in addition to hysterectomy and adnexectomy; bowel resection, for example, is often also indicated. In the case of cancer restricted to the uterine appendages, pelvic and para-aortic lymph nodes are also excised. The staging of ovarian cancer is based on several tissue samples.
If it is evident from examinations performed during the diagnostic stage that complete surgical removal of cancer tissue is not possible, neoadjuvant chemotherapy is started and surgery considered at a later stage depending on the response.
Adjuvant cytostatic therapy is used in most cases after surgery. The first-line cytostatic chemotherapy for epithelial ovarian cancer is a combination of paclitaxel and carboplatin.
Predictive factors that influence the prognosis include the following: volume of residual disease after surgery, age of the patient, stage of the disease, histological type and response to first-line chemotherapy.
Recurrent cancer is treated with cytostatic drugs. In some cases, surgical excision of single malignant lesions or radiotherapy may be considered. Today, there are also medicinal options for maintenance treatment.
Fertility-sparing surgery may be performed in carefully selected cases, provided that the disease is confined to the ovary/ovaries.
Follow-up
Ovarian cancer has a significant tendency to recur as early as within 3 years from the beginning of treatment. Recurrence most often occurs in the abdominal cavity or in lymph nodes.
The patient is followed up in specialized care for 3-5 years after the end of treatment.
There is no evidence-based recommendation for optimal follow-up of asymptomatic patients.
A primary care follow-up visit should consist of the patient's history, general and gynaecological examinations.
In specialized care, ultrasonography, and supplementary imaging depending on the symptoms and findings, as necessary
Prognosis
The overall 5-year survival rate in epithelial ovarian cancer is 50%. Where the cancer is confined to the ovaries, 80-90% of patients will survive. The majority of cancers are detected at an advanced stage in which case the 5-year survival rate is 20-30%.