Table of Contents
Diagnosis of Cervical Cancer
Anamnesis and clinical evaluation of cervical cancer
In anamnesis, it is important to check for symptoms. As pre– and early stages of cervical cancer are usually asymptomatic, they usually represent a random finding. In 90% of the cases, however, advanced cancers show symptoms like contact bleeding, lymphoedema of the legs, ureteral stenosis, ileus symptoms or back pain.
Gynecological examination in cervical carcinoma
Though the recommended age at first screening suggested by WHO is 30 years, age at first screening varies between countries. In Germany, it’s 20 years, and in the US it’s 21. Screening includes the direct visualization of the cervix by adjusting the speculum and using acetic acid or Lugol’s iodine to highlight precancerous lesions so they can be viewed with the “naked eye”, assessment of epithelial atypia on the portio surface or the cervical canal and the cytological smear diagnostics.
In this case, smears are taken from the endo- and ectocervix and then evaluated microscopically according to Papanicolaou staining ( ‘Pap smear’).
In addition, colposcopy can be performed, in which the portio is viewed through a colposcope in 6 to 40-fold magnification. For an extended investigation, the portio can be dabbed with acetic acid or Lugol-iodine solution (Schiller-iod sample). In the case of the latter, the normal epithelium becomes brown, while atypical, altered epithelium remains bright.
A detailed description of the various diagnostic steps of gynecological examination can be found here: Diagnostics of female genitalia.
The following abnormal findings indicate the presence of atypia:
|Cytological smear||Changes in the nucleus (e.g., polymorphic, multiple nuclei), changes in the plasma, a shift of the nuclear-plasma ratio in favor of the nucleus|
|Colposcopy||Vesicular epithelium, mosaic, puncture, bleeding nodular surface, ulcer, exo- or endophytic tumor|
Further Studies in Cervical Cancer
An HPV infection can be detected by PCR test. Since papillomaviruses are found in 98% of the invasive carcinomas, a negative test result almost excludes an oncological hazard. However, a positive finding only indicates a potential disease risk. Thus, HPV diagnostics are suitable for supplementary examination in suspicious findings, but not as a screening method.
In the case of significant findings, it is necessary to confirm them histologically. Here tissue is taken from suspicious areas. This can be done by selective biopsy under a colposcopy or cervical curettage.
Another, a more invasive method is conization. In this case, pathological tissue, which should contain both the endocervix and the ectocervix, is removed either by means of a scalpel (knife conization) or electric loop (loop conization, LEEP). Because of the typical tumor localization (sexually mature women: portio surface, older women: cervical canal), the cones taken should be flat in premenopausal women and high and narrow in postmenopausal cases. Disadvantage of this method is the risk of bleeding and late complications, such as cervical stenosis and insufficiency.
In addition to direct visualization of the cervix via a speculum and palpation, the evaluation of the spread of the tumor is also mandatory in histologically confirmed cancer. For this purpose, transvaginal and renal ultrasounds should be performed.
Stage 1A Stage 1B
Stage 2A Stage 2B Stage 3B
Stage 4A Stage 4B
FIGO STAGING SYSTEM
Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation (feeling with the fingers), inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization.
An MRI is also considered:
Patients with histologically confirmed cervical cancer FIGO stage from 1B2 up to and including III should receive a baseline MRI for the assessment of locoregional tumor spread.
If necessary, rectoscopy and cystoscopy can be performed and, in FIGO IB2, a CT of thorax and abdomen can be used to assess the extrapelvic tumor spread.
Therapy of Cervical Cancer
The therapy of cervical cancer consists in a complex individual treatment planning, which must be adapted to the individual case. In addition to the stage classification, factors such as child planning, patient age, and risk factors play a role.
Treatment of cervical intraepithelial neoplasia (CIN)
The spontaneous recovery rate of CIN I and II is high, which is why follow-up cytology should be performed after three months.
If the changes remain over 12 months or if a CIN III is present, an operative therapy must be considered.
Most frequently carried out is conization (see above). The cut margins are then assessed histologically: if they are free from atypia, the probability of recurrence for a CIN is 1-2%; if atypia is found, they are 15-20%.
Another method is laser surgery, in which the pathological tissue is destroyed by a laser beam at a depth of 5 to 7 mm. This method is only slightly invasive, but a histological assessment is not possible.
In case of postmenopausal women, completed family planning or other diseases of the uterus, a hysterectomy is considered.
Treatment of early stages of cervical cancer
Cancer with early stromal invasion can be cured by a hysterectomy (see below). In the case of a microcarcinoma (FIGO 1A2), the removal of the pelvic lymph nodes is also considered. If a child’s wish is required, conization can be sufficient.
Surgical Treatment of Invasive Cervical Cancer
Abdominal radical operation
Operative therapy is the therapy of choice in the FIGO stages IB-IIB. Radical hysterectomy (abdominal radical surgery) is used as standard.
Depending on the present tumor findings, a different radicality of the operation is to be sought. According to Piver et al., there are the following stages:
|Grade I||Restricted Radicality: Extrafascial hysterectomy without complete mobilization of ureters|
|Grade II||Modified-radical hysterectomy = extrafascial hysterectomy with resection of parametria medial to the ureters: discontinuation of the uterine artery to the crossover of the ureter and the ligg. uterosacralia / cardinalia halfway to the crossbones / pelvic wall. Resection of the upper vaginal third and preparation of the ureter (without detachment from lig. pubovesicale).|
|Grade III||“Classical” radical hysterectomy (equivalent to Wertheim-Meigs operation): discontinuation of the uterine artery at the origin and the ligg. uterosacralia and cardinalia close to origins (Os sacrum, pelvic wall). Resection of the upper vaginal third (up to the vaginal half) and preparation of the ureter (up to the mouth in the bladder, while preserving a small lateral portion of the lig. pubovesicale).|
|Grade IV||Like grade III, in addition, complete release of the ureters from Lig. pubovesicale (a). Resection of the A. vesical superior (b) and up to 3/4 of the vagina (c).|
|Grade V||Resection of parts of the bladder or distal ureter with ureteral implantation|
The removal of the uterus with parametrium and vaginal cuff through pelvic lymphadenectomy is called Wertheim-Meigs operation and is most frequently performed in Germany. In pelvic lymph nodes and larger carcinomas, which are positive at frozen sections, para-aortic lymphadenectomy should be performed.
If a squamous cell carcinoma is present, the removal of the adnexa is not necessary for premenopausal women. In the case of adenocarcinoma, however, this should be considered. The reason is the higher metastasis probability.
After a radical hysterectomy, the occurrence of the following complications is possible: fistulae (bladder-vagina, ureter-vagina), lymphedema, lymphoceles, bladder emptying disorders, and ureteral stenoses.
A less invasive alternative is laparoscopic lymphadenectomy followed by radical vaginal hysterectomy.
In the case of small tumors (<2 cm), negative lymph nodes and squamous cell carcinoma as a type of tumor, trachelectomy (cervicectomy) can be performed to maintain the ability to bear children. In doing so, the uterus and a part of the cervix are left behind and attached to the vagina. The removal of the lymph nodes is performed laparoscopically.
In FIGO stage IV, an exenteration may be considered. The vagina, urinary bladder, and uterus (anterior exenteration) or vagina, rectum, uterus (posterior exenteration) and stoma system are removed depending on the disease.
Radiotherapy for cervical cancer
When the cervical limits (FIGO stage III) are exceeded, a primary surgical procedure can not be attempted. Here, primary radiation therapy with a combination of platinum-based chemotherapy (cisplatin) is the method of choice. It may be indicated as of stage IIB.
Optimal radiotherapy results are achieved by a combination of teletherapy (percutaneous irradiation) and brachytherapy (contact therapy).
In brachytherapy, a radionuclide carrier is introduced into the cavum uteri by the afterloading method. In this way, surrounding structures such as urinary bladder and rectum are spared.
In case of inoperable patients, or if preservation of the ovarian function is not attempted, primary radiotherapy can also be performed in smaller carcinomas, since this is equivalent to the operation.
Postoperative irradiation is indicated when the carcinoma can not be completely removed by surgery.
Complications of radiation therapy may include: colpitis, cystitis, proctitis, dyspareunia, fistula (vagina-bladder, vagina-rectum) and loss of ovarian function.
Chemotherapy for cervical cancer
In contrast to other genital carcinomas (e.g., ovarian carcinoma), cervical carcinoma is less responsive to chemotherapy. In stage IVB, palliative system therapy is the means of choice.
Neoadjuvant chemotherapy can be used to reduce the tumor size (down-staging) prior to surgery or irradiation.
Aftercare and Prognosis of Cervical Cancer
Tumor aftercare in case of cervical cancer
For aftercare, the current guidelines recommend the following:
Women who have had a total hysterectomy (removal of the uterus and cervix) should stop screening. Women who have had a supracervical hysterectomy (cervix intact) should continue screening according to guidelines. (American cancer society (ACS), American society for colposcopy and cervical pathology (ASCCP), and American society for clinical pathology (ASCP); 2012)
Optional studies include colposcopy, vaginal ultrasound, renal ultrasound and HPV testing.
Control of tumor markers (SCC, CEA) is not recommended due to a lack of evidence.
Prognosis in cervical cancer
The prognosis of cervical cancer depends on various factors, including tumor stage, lymph node involvement, resection margins, and tumor size. Thus the mean 5-year survival rates of the different stages differ as follows:
- Stage I: 80 %
- Stage II: 70 %
- Stage III: 45 %
- Stage IV: 15 %
If vascular invasion occurs, the 5-year survival rate drops from 80% to 30%, in the case of lymph node metastasis from 85% to 50%. Young age is also a negative prognostic factor.
Prevention of Cervical Cancer
Primary prevention of cervical cancer
Primary prevention of cervical carcinoma involves the prevention of risk factors (promiscuity, smoking, infections) and the possibility of vaccination against HPV viruses. This should be done as early as possible and before the start of sexual activity. It is indicated for girls and boys alike.
The following vaccines are currently available:
- Gardasil: against HPV 6, 11, 16, 18
- Cervarix: against HPV 16, 18
Secondary prevention of cervical cancer
Secondary prevention is used to detect already existing atypia. This includes the screening test, which can be claimed once a year by women from the age of 21, including a cytologic smear (see above).
1. Which statement regarding cervical cancer is correct?
- A positive finding in HPV diagnostics indicates advanced cervical cancer.
- In the case of conization, the removed conus should be flat in postmenopausal women and high and narrow in premenopausal cases.
- Treatment of cervical cancer is always based on a standard treatment plan independent of individual factors.
- Adnectomy is obligatory for any surgical method.
- The HPV vaccine is part of the primary prevention of cervical cancer.
2. Which diagnostic method for early detection of cervical cancer or pre-therapeutic classification does not make sense?
- Cytological smear
- Radiological examination
- Speculum evaluation
- Transvaginal ultrasound
- MRI investigation
3. A 28-year-old female (0 Gravida, 0 Para) consults her gynecologist because of contact bleeding after sexual intercourse. After a detailed diagnosis, cervical carcinoma is found in FIGO stage III. What is the most effective therapy?
- Chemotherapy alone
- Knife conization
- Radical hysterectomy with pelvic lymphadenectomy without removal of the adnexa
- Radical hysterectomy with pelvic lymphadenectomy with removal of the adnexa
- Radiotherapy in combination with platinum-containing chemotherapy