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Cervical Dysplasia

Image: “Cervical Dysplasia.” by Blausen Medical Communications, Inc. Licence: CC BY 3.0


 

Diagnosis of Cervical Cancer

Clinical evaluation of cervical cancer

Because pre-malignant 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, such as contact bleeding, lymphedema of the legs, ureteral stenosis, ileus symptoms, or back pain.

Gynecologic examination in cervical carcinoma

The recommended age at first screening suggested by the World Health Organization (WHO) is 30 years. However, the age at first screening varies between countries. It is 20 years in Germany, and 21 years in the USA. Screening includes direct visualization of the cervix by adjusting the speculum and using acetic acid or Lugol’s iodine to highlight precancerous lesions, assess epithelial atypia on the vaginal portion of the cervix or ectocervix(portio vaginalis cervicis), and cytologic evaluation of the cervical smear.

In this case, smears are obtained from the endocervix and the ectocervix for microscopic evaluation via Papanicolaou staining (‘Pap smear’).

In addition, a colposcopy can be used to view the ectocervix under a 6- to 40-fold magnification. For an extended investigation, the ectocervix is dabbed with acetic acid or Lugol’s iodine. In the case of the latter, the normal epithelium turns brown, while the atypical, altered epithelium remains bright.

colposcopy

Image: Illustration demonstrating a colposcopy. By BruceBlaus, Licence: CC BY-SA 4.0

The various diagnostic steps in the gynecological examination are found here: Diagnostics of female genitalia.

Abnormal findings indicate atypia:

Diagnostics Findings
Cytological smear Changes in the nucleus (e.g., polymorphic, multiple nuclei), changes in the plasma, a shift in the nuclear-to-plasma ratio in favor of the nucleus
Colposcopy Vesicular epithelium, mosaic, puncture, bleeding nodular surface, ulcer, exophytic or endophytic tumor

Further Studies in Cervical Cancer

HPV diagnostics

HPV infection can be detected using a PCR. Because papillomaviruses are found in 98% of invasive carcinomas, a negative test result almost excludes oncologic risk. However, a positive finding only indicates potential disease risk. Thus, HPV diagnostics are indicated for supplementary examination in suspicious findings, but not as a screening method.

hpv

Image: In most cases, cells infected with the HPV virus heal on their own. In some cases, however, the virus continues to spread and becomes invasive cancer. By OpenStax College, License: CC BY 3.0

Histology

Any significant findings associated with suspicious cases must be confirmed histologically via selective biopsy under colposcopy or cervical curettage.

Conization is a more invasive method entailing the removal of pathological tissue containing both the endocervix and the ectocervix, using a scalpel (knife conization) or electric loop (loop conization, LEEP). Because of the typical tumor localization (sexually mature women: ectocervix; older women: cervical canal), the cones are flat in premenopausal women and high and narrow in postmenopausal cases. However, this method is associated with the risk of bleeding and late complications, such as cervical stenosis and insufficiency.

Pre-therapeutic staging

In addition to direct visualization of the cervix via a speculum and palpation, the evaluation of tumor spread is also mandatory in histologically-confirmed cancer. Therefore, transvaginal and renal ultrasound is performed.

vaginal_ultrasound

Image: Transvaginal ultrasonography procedure. By BruceBlaus, Licence: CC BY-SA 4.0

Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on a clinical examination, rather than surgical findings. The diagnosis is based on staging using the following tests: palpation (feeling with the fingers); inspection; colposcopy; endocervical curettage; hysteroscopy; cystoscopy; proctoscopy; intravenous urography; X-ray examination of the lungs and skeleton; and cervical conization.

Indications for MRI

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. In FIGO IB2, a CT of the thorax and abdomen can be used to assess extrapelvic tumor spread.

Therapy of Cervical Cancer

Therapy of cervical cancer is tailored to individual cases and entails complex individual treatment planning. In addition to the stage classification, factors such as family planning, patient age, and risk factors are considered.

Note: The therapy of cervical cancer must be adapted to each patient individually!

Treatment of cervical intraepithelial neoplasia (CIN)

The spontaneous recovery rate of CIN I and II is high, and therefore, follow-up cytology is needed after 3 months.

Changes persisting beyond 12 months or the presence of CIN III warrant operative therapy.

Conization is the most frequently performed treatment. The cut margins are assessed histologically, and in the absence of atypia, the probability of CIN recurrence is 1–2% however, cut margins with atypia increase the risk of CIN by 15–20%.

Laser surgery is another option, in which the pathologic tissue is destroyed by a laser beam at a depth of 5–7 mm. This method is only slightly invasive, but a histologic assessment is not possible.

A hysterectomy is considered in cases of postmenopausal women, and women who have undesired fertility or are diagnosed with other diseases of the uterus.

Treatment of early stages of cervical cancer

Cancer with early stromal invasion can be cured by hysterectomy (see below). In the case of a microcarcinoma (FIGO 1A2), the removal of the pelvic lymph nodes is another option; however, women contemplating pregnancy and childbirth may undergo conization alone.

Surgical Treatment of Invasive Cervical Cancer

Abdominal radical operation

Operative therapy is the therapy of choice in FIGO stages IB-IIB. Radical hysterectomy (abdominal radical surgery) is the standard.

Depending on the tumor findings, different grades of radical surgery are indicated. According to Piver et al., the following procedures are performed:

Grade I Restricted radicality: Extrafascial hysterectomy without the complete mobilization of the ureters
Grade II Modified-radical or extrafascial hysterectomy with resection of parametria medial to the ureters: ligation of the uterine artery at the crossover of the ureter over the uterosacral and cardinal ligaments halfway to the crossbones / pelvic wall; resection of the upper vaginal third and preparation of the ureter (without detachment from the pubovesical ligament).
Grade III ‘Classical’ radical hysterectomy (equivalent to Wertheim-Meigs operation): ligation of the uterine artery at the origin and of the uterosacral and cardinal ligaments close to their origins (Os sacrum, pelvic wall); resection of the upper 1/3 of the vagina (up to 1/2) and preparation of the ureter (close to the mouth of the bladder, while preserving a small lateral portion of the pubovesical ligament).
Grade IV Similar to grade III, complete release of the ureters from pubovesicle ligament (a); resection of the superior vesicular artery (b) and up to 3/4th 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 known as Wertheim-Meigs operation. In positive pelvic lymph nodes and larger carcinomas, that are margin positive on the frozen section, para-aortic lymphadenectomy is performed.

In the case of squamous cell carcinoma, the removal of adnexa is not necessary for premenopausal women. In the case of adenocarcinoma, however, it should be considered because of the higher risk of metastasis.

Note: Removal of the adnexa is not obligatory!

Radical hysterectomy may be associated with the risk of following complications: fistulae (bladder-vagina, ureter-vagina), lymphedema, lymphoceles, bladder emptying disorders, and ureteral stenosis.

Alternative Operations

hysterectomy

Image: Hysterectomy. By BruceBlaus, Licence: CC BY-SA 4.0

A less invasive alternative is laparoscopic lymphadenectomy followed by radical vaginal hysterectomy.

Diagram showing the parts removed with trachelectomy surgery.

Image: Diagram showing the parts removed with trachelectomy surgery. By Cancer Research UK, Licence: CC BY-SA 4.0

In the case of small tumors (< 2 cm), negative lymph nodes and squamous cell carcinoma, trachelectomy(cervicectomy) are indicated to preserve fertility. The uterus and a part of the cervix are left behind and attached to the vagina. Removal of the lymph nodes is performed laparoscopically.

In FIGO stage IV, 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 tumor extends beyond the cervix limits (FIGO stage III) are exceeded, a primary surgical procedure is not feasible. Instead, primary radiation therapy with a combination of platinum-based chemotherapy (cisplatin) is the method of choice starting with stage IIB.

Optimal radiotherapy results are achieved via a combination of teletherapy (percutaneous irradiation) and brachytherapy (contact therapy).

Brachytherapy for cervical cancer

Image: Brachytherapy for cervical cancer. By Cancer Research UK, Licence: CC BY-SA 4.0

In brachytherapy, a radionuclide carrier is introduced into the cavum uteri using the afterloading method, which spares surrounding structures, such as the urinary bladder and rectum.

In cases that are inoperable, or if preservation of ovarian function is not the goal, primary radiotherapy is also indicated for smaller carcinomas because this is equivalent to the operation.

Postoperative irradiation is indicated when the carcinoma cannot be completely obliterated 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 systemic 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:

Screening cessation for women undergoing total hysterectomy (removal of the uterus and cervix); continued screening of women who were treated with supracervical hysterectomy (cervix intact).

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. The mean 5-year survival rates of the different stages are:

  • Stage I: 80%
  • Stage II: 70%
  • Stage III: 45%
  • Stage IV: 15%

If vascular invasion occurs, the 5-year survival rate drops from 80%–30%, and in the case of lymph node metastasis from 85%–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, and infections) and possible vaccination against HPV viruses as early as possible and before the start of sexual activity. It is indicated for girls and boys alike.

The currently available vaccines include:

  • Gardasil against HPV 6, 11, 16, and 18
  • Cervarix against HPV 16 and 18

Secondary prevention of cervical cancer

Secondary prevention is used to detect pre-existing atypia via annual screening tests (cytological smears) in women starting at age 21 years.

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