Cervical cancer during pregnancy is a malignant neoplasm that originates from the transformation zone, exocervix, endocervix and is detected during pregnancy. In more than two-thirds of cases, it is asymptomatic. With a manifest course, it is manifested by contact bleeding, spontaneous vaginal bleeding, leukorrhea, pain in the lower abdomen, violation of the function of the pelvic organs. It is diagnosed on the basis of gynecological examination, PCR, cytological analysis, colposcopy, histology of the biopsy. Organ-preserving and radical surgical interventions, radiation and chemotherapy are used for treatment.
ICD 10
C53 Malignant neoplasm of the cervix
General information
Cervical cancer (CC) is the most common oncopathology detected in pregnant women. 1-3% of the disorder is diagnosed in the gestational period. Depending on the region, the prevalence of the disease ranges from 1.2 to 10 cases per 10,000 pregnancies. Gestation occurs in 3.1% of patients with a previously established diagnosis of cervical cancer during pregnancy. The disease is more often detected in sexually active smoking women who have started an intimate life before the age of 16, have more than 2-3 sexual partners per year, are infected with the human papillomatosis virus (HPV), and often with other genital infections (chlamydia, trichomoniasis, syphilis, gonorrhea, ureaplasmosis).
Causes of cervical cancer during pregnancy
In the vast majority of cases, malignant degeneration of the mucosa of the exo- and endocervix begins long before gestation. Neoplasia is associated with human papillomatosis viruses transmitted through sexual contact. DNA-containing papillomatous viruses are detected in 95% of patients with a confirmed diagnosis of cervical cancer. In 65-75% of cases, viral agents of 16 and 18 serotypes are considered to be the provoking factor, less often HPV 31, 33, 35, other types of high and medium risk. HPV infection in the female population is 5-20%. In most patients, the virus persists for a long time without any clinical manifestations.
The factors contributing to an increase in its pathogenicity and the onset of cancer have not yet been identified. Despite the theoretical possibility of accelerating carcinogenesis against the background of a physiological decrease in immunity during pregnancy, there are no convincing data on the negative effect of gestation on the course of the malignant process in the cervix to date. Moreover, according to the observations of specialists in the field of oncogynecology, two thirds of pregnant women have a regression of precancerous conditions.
The detection of cervical cancer during gestation is favored by a number of circumstances. Firstly, many patients from the risk group outside of pregnancy rarely visit medical institutions for preventive purposes. Registration in a women’s clinic in order to receive medical care and social benefits involves regular monitoring by a specialist and performing screening examinations, during which cancer may be detected. Secondly, by the 20th week of gestational age, most pregnant women have an outward shift of the transformation zone and the junction of the cylindrical cervical epithelium with the flat vaginal epithelium. As a result, the area of the cervical mucosa, most often affected by cancer, becomes clearly visible and accessible for cytological screening, colposcopy and other studies.
Pathogenesis
Although the probability of infection with papillomavirus infection reaches 75%, in 90% of women, the immune system quickly eliminates the pathogen. In 10% of cases, viral particles persist in basal epithelial cells and can regress. Only in some patients, under the influence of unidentified factors, HPV begins to progress. Virus DNA is embedded in the genome of cervical epithelial cells, which leads to disruption of the mechanisms of apoptosis and malignant morphological transformation — from mild to moderate dysplasia to pronounced dysplastic changes and carcinoma in situ. The viral genes E5 and E6 have a blocking effect on the anti-oncogenes p53 Rb of normal cellular elements of the cervix.
Due to the inactivation of the tumor suppressor, uncontrolled proliferation of tumor cells is triggered. In addition, under the influence of a protein in the synthesis of which the E6 gene participates, telomerase is activated, which contributes to the emergence of immortal cell clones and the development of tumors. Simultaneously, due to blocking of cyclin-dependent kinase p21 and p26 by the protein produced by the E7 gene, active division of damaged cells begins. Subsequently, cancer cells spread from the mucosa to other tissues of the uterine neck, the tumor grows into adjacent organs and metastasizes.
Classification
The systematization of forms of cervical cancer during pregnancy is based on the same criteria as in non-pregnant patients. Taking into account the type of the affected epithelium, tumors can be exophytic squamous, originating from the exocervix (detected in 53.6% of pregnant women), endophytic adenocarcinomatous, formed by endocervix cells (diagnosed in 25.7% of patients). In 20.7% of cases, cervical neoplasia during gestation is mixed. To develop optimal pregnancy management tactics, it is important to take into account the stage of cancer:
- Stage 0. In precarcinoma (in situ tumors), the process is localized in the epithelial layer, cell atypia corresponds to the borderline state between grade III dysplasia and true malignant neoplasia. The prognosis for pregnancy is the most favorable, minimally invasive operations are possible after childbirth.
- Stage I. Cancer does not go beyond the neck. The tumor focus is determined microscopically (IA, microinvasive cancer) or macroscopically (IB). It is possible to continue gestation and natural delivery with the consent of the patient with the implementation of conservative or radical interventions in the postpartum period.
- Stage II. The carcinoma has spread to the body of the uterus, the upper part of the vagina (IIA) and the parametrium (IIB). The walls of the pelvis and the lower third of the vagina are not involved in the process. With a gestational term of more than 20 weeks, pregnancy can be prolonged for no more than 8 weeks until the fetus reaches viability and is completed by cesarean section.
- Stage III. The cancer has spread to the lower third of the vagina (IIIA), reaches the walls of the pelvis, possible blocking of the kidney and the occurrence of hydronephrosis (IIIB). It is recommended to start treatment as early as possible. In the 1st trimester, pregnancy is interrupted, in the 2nd — 3rd, a caesarean section is performed with extended extirpation of the uterus.
- Stage IV. The cancer process involves the mucosa of the rectum and bladder, or the tumor has gone beyond the pelvis (IVA), there are distant metastases (IVB). During pregnancy, it is rare. Detection of an inoperable tumor is the basis for cesarean section with a viable fetus, followed by radiation and chemotherapy.
Symptoms of cervical cancer during pregnancy
Preinvasive and minimally invasive forms of neoplasia, detected in 70% of pregnant women, are asymptomatic. Women with the initial stages of invasive cancer (IB, IIA) have contact spotting after vaginal examination, sexual intercourse. Bleeding from damaged neoplasia vessels in the first trimester is often mistakenly regarded as a threatening spontaneous miscarriage, in II-III — as premature detachment or placenta previa. The appearance of transparent whites is possible. With tumors with decay, the discharge becomes fetid.
Pain in the lower abdomen, taken as a threat of termination of pregnancy, rarely occurs. The appearance of soreness in the lumbosacral region, buttock, back of the thigh usually indicates infiltration of pelvic tissue. When the ureteral tumor is squeezed, the outflow of urine is disrupted, with the germination of the bladder, rectum, the appearance of blood impurities in urine and feces, their discharge through the vagina is observed.
Complications
With invasive cancers, the likelihood of spontaneous termination of gestation by miscarriage or premature birth increases. Significant deformation of the organ by the tumor can provoke the development of isthmic-cervical insufficiency. In patients with bleeding neoplasia, anemia of pregnant women is more pronounced. The perinatal mortality rate rises to 11.5%. Termination of pregnancy by natural childbirth in the presence of a large volumetric neoplasm significantly increases the likelihood of uterine neck ruptures, massive postpartum bleeding, hematogenous cancer metastasis. Therefore, in such cases, a caesarean section is recommended.
Diagnostics
The main tasks of the diagnostic search are to exclude or confirm the malignancy of the pathological process and to accurately determine the stage of cancer. During gestation, it is recommended to use examination methods that do not pose a threat to the fetus, which complicates the correct diagnosis. The most informative are:
- Examination on the chair. Examination in mirrors makes it possible to detect macroscopically visible changes in the exocervix, the transformation zone, to detect neoplasms protruding into the vaginal cavity from the cervical canal. It is possible to detect contact bleeding neoplasia.
- PCR screening for HPV. Although infection with the papilloma virus does not indicate a cervical tumor, receiving a positive test increases cancer alertness. PCR diagnostics makes it possible to determine the spectrum of serotypes of the pathogen, to type them.
- Cytology of cervical scraping. During pregnancy, the sampling of the material is carried out with caution to prevent bleeding, preserve the cervical plug, and exclude damage to the fetal membranes. The study is aimed at determining dysplasia, atypia, malignancy.
- Colposcopy. Complements the results of the cytological test. Extended colposcopy is performed in the presence of laboratory signs of a precancerous or cancerous condition to detect a pathological focus in the mucous membrane of the neck before performing a targeted biopsy and monitoring the material intake.
- Histological examination of the biopsy. It is used to determine the type of tumor and the degree of its differentiation. To reduce the traumatization of the uterine neck and reduce the likelihood of bleeding, a wedge-shaped biopsy is usually performed in pregnant women. According to many obstetricians and gynecologists, the material should not be taken earlier than the 2nd trimester.
To assess the condition of the rectum, pelvic tissue, bladder, regional lymph nodes, pelvic ultrasound, cystoscopy, rectoromanoscopy, MRI of individual organs, MRI of lymph nodes can be recommended. If metastases are suspected, an MRI of the whole body is the preferred method of examination. Radiation diagnostic methods for pregnant women with suspected uterine cervical cancer are prescribed only because of the possible damaging effect on the fetus. The disease is differentiated with erosions, polyps, condylomas, cysts, cervicitis, ectopia, ectropion, dysplasia, vaginal tumors, spontaneous miscarriage, placenta previa. The patient is examined by an oncogynecologist, according to indications — a urologist, a proctologist.
Treatment of cervical cancer during pregnancy
The choice of medical tactics depends on the gestational age, the stage of the neoplastic process, and the patient’s reproductive plans. Preservation of gestation, regardless of the time of cancer detection, is possible only with neoplasms of stages 0 and IA (with stromal invasion up to 3 mm). With stage IA tumors with stroma invasion to a depth of 3 to 5 mm, stage IB and II neoplasms in the 1st trimester, termination of pregnancy is indicated, from 13 to 20 weeks – radical surgery, after 20 weeks — prolongation of pregnancy to 28-32 weeks with condition monitoring, operative delivery and simultaneous radical hysterectomy. Patients who decide to continue gestation are accompanied by an oncogynecologist.
Stage III-IV cancer is an indication for termination of gestation at any time. Up to the 20th week, external radiation therapy is prescribed, provoking spontaneous miscarriage at a dose of 4000 sGr. After 20 weeks, cesarean section and subtotal resection of the uterus are performed regardless of the viability of the fetus. The main methods of treatment for uterine cervical cancer in pregnant women are the same as outside the gestational period:
- Organ-preserving operations. They are indicated for young patients with in situ carcinoma and stage IA cancer (with penetration into the stroma no deeper than 3 mm) who want to preserve fertility. Conization is performed 4-8 weeks after a medical abortion or 7-9 weeks after vaginal or abdominal delivery.
- Simple hysterectomy. Removal of the uterus with the preservation of appendages is recommended for women with preinvasive and minimally invasive cancer who do not have reproductive plans. The operation is performed as an independent intervention in the first trimester and simultaneously with a cesarean section when deciding to carry out pregnancy.
- Extended hysterectomy. It is the operation of choice for stage IB-II cancer. In the 1st trimester, it is carried out, including for termination of pregnancy, in the 2nd and 3rd, it is performed simultaneously with surgical delivery. After 2-3 weeks, adjuvant radiation therapy is recommended for the woman.
- Combined chemoradiotherapy. It is used for malignant neoplasm of the cervix of the III-IV stages. External irradiation allows not only to affect the tumor process, but also to interrupt gestation up to 20 weeks. Chemotherapy drugs and radiomethodes are not used when a woman decides to save the fetus.
Prognosis and prevention
When a pregnant woman is diagnosed with cervical cancer, the prognosis is always serious. The best results can be achieved with non-invasive forms of neoplasia. The five-year survival rate of patients with stage I cancer detected during pregnancy does not differ from the same indicator for non-pregnant women and reaches 88%. With a stage II tumor, up to 54% of cancer patients survive for 5 years (against 60-75% of women with diagnosed uterine cervical cancer outside pregnancy), with stage III — up to 30-45%. In invasive tumors, delaying treatment due to the desire to preserve pregnancy worsens the survival prognosis by 5% for each month of prolonged gestation.
After organ-preserving operations, cancer recurs in 3.9% of patients, and a new pregnancy occurs in 20.0-48.4%. The long-term consequences of conization are isthmic-cervical insufficiency, infertility, the formation of rectovaginal, urethro- and vesicovaginal fistulas. Prevention provides for compliance with the rules of sexual hygiene using methods of barrier contraception, refusal of promiscuous sexual relations, regular dispensary observation of HPV-infected patients, timely treatment of precancerous conditions.
