Gynecologic cancers

ALSO KNOWN AS: Cervical cancer, uterine cancer, ovarian cancer, gestational trophoblastic disease, and cancers of the vulva, vagina, and Fallopian tubes

RELATED CONDITIONS: Cancer of the colon and rectum, cancer of the bladder, peritoneal carcinomatosis

DEFINITION: Gynecologic cancers are cancers that arise in one of the anatomic structures of the female reproductive tractthe Fallopian tubes, the ovaries, the uterus, the cervix, the vagina, and the vulva. Historically, cancer of the breast has not been considered to be a gynecologic cancer.

Risk factors: Risk factors for cervical cancer include a woman having her first sexual encounter at less than age fifteen, multiple sexual partners, promiscuous male partners, a history of sexually transmitted diseases, an impaired immune system, and cigarette smoking.

Risk factors for uterine cancer are use of medications containing estrogen without the addition of progesterone (the so-called unopposed estrogen effect), use of the medication tamoxifen for more than two years, onset of late menopause (over fifty-two), obesity, never having had children (nulliparity), diabetes, high blood pressure, and increased dietary fat intake as well as having had estrogen-secreting ovarian tumors, polycystic ovarian syndrome, or radiation therapy to the pelvis.

Risk factors for ovarian cancer are not having been pregnant, incessant ovulation (ovulation not interrupted by oral contraceptives or pregnancy), a family history of ovarian cancer, breast cancer, and exposure to talc.

A for cancer of the vulva is exposure to the human papillomavirus (HPV).

Risk factors for cancer of the vagina include age, HPV infection, exposure to diethylstilbestrol (DES), a history of cervical cancer, vaginal adenosis, uterine prolapse, cigarette smoking, chronic vaginal irritation, low socioeconomic status, hysterectomy at an early age, and vaginal trauma.

The major risk factors for cancer of the Fallopian tube are chronic inflammation in the form of endometriosis or pelvic infections, a history of infertility, and low parity (no children or only one or two).

The primary risk factors for gestational trophoblastic disease are being over age forty or less than age twenty and having a history of a prior molar pregnancy.

Etiology and the disease process: What is known about the etiology of gynecological cancers varies. Cancer of the Fallopian tube and ovary share abnormalities of the cancer genes TP53 and ERBB-2, suggesting similar genetic risks and environmental factors. HPV causes cervical cancer and is believed to cause changes that progress to cancer of the vulva. If left untreated, up to one-third of women infected with HPV will develop cervical cancer. Women who have long-term unopposed estrogen stimulation undergo changes in the endometrium that can precede the development of uterine cancer.

Most vaginal cancers are metastatic, originating from cancers of the cervix or vulva and spreading to the vagina, although metastases have been reported to occur from the uterus, ovaries, colon, rectum, breast, and even the kidney.

Gestational trophoblastic disease, which can mimic a normal pregnancy, progresses rapidly and is fatal if not treated but has a good prognosis with treatment. Ovarian cancer is an insidious disease, and with the lack of screening and the associated vague symptoms, most cases are advanced at the time of diagnosis.

Incidence: Cancer of the uterus is among the most common cancers involving the female reproductive tract. Globally, there are approximately 420,000 new cases of uterine cancer each year, with about 68,000 occurring in the United States. A woman’s lifetime risk of cancer of the uterus is about 1 in 50. Ovarian cancer is the second most common cancer involving the female reproductive tract and is the leading cause of death of all gynecologic cancers. There are approximately 26,000 new cases diagnosed each year and 16,000 deaths. The lifetime risk for ovarian cancer is 1 in 87. Cervical cancer is also a common gynecological cancer, with 660,000 new global cases and 14,000 new cases in the United States per year.

Less common cancers are those of the vagina, accounting for 1 to 2 percent of gynecological cancers, and cancer of the vulva, accounting for 0.3 to 0.7 percent of gynecological cancers. Fallopian tube cancer is also rare, accounting for approximately 1 percent of all gynecologic malignancies. Gestational trophoblastic disease occurs in 1 to 2 births of 1,000 pregnancies in the United States.

Symptoms: Many gynecologic cancers share symptoms such as abnormal bleeding. However, some are much harder to detect. Abnormal bleeding through the vagina is the most common symptom associated with cancer of the uterus, occurring in approximately 90 percent of cases. For premenopausal women, this may include breakthrough bleeding, bleeding, or heavy bleeding, all of which reflect an underlying hormonal imbalance. For postmenopausal women, any bleeding should be considered abnormal and should be evaluated by a gynecologist. Abnormal uterine bleeding is the most frequent symptom of gestational trophoblastic disease. The most common symptoms associated with cancers of the vagina are abnormal bleeding or an excessive, non-odorous, watery discharge. Less frequent symptoms include pelvic pain, an increased frequency of urination or pain with urination, and constipation. Cancer of the Fallopian tube, for the most part, is a disease without specific symptoms. Symptoms associated with cancer of the Fallopian tube include an abnormal, watery vaginal discharge or excessive bleeding. Pain and a palpable pelvic mass are infrequently associated with Fallopian tube cancer. For cancer of the vulva, irritation and itching are the most common symptoms.

Cervical and ovarian cancer are harder to detect through symptoms. An abnormal Pap smear is the earliest “symptom” of cervical cancer, as most patients with cervical cancer are physically asymptomatic. In more advanced cases of cervical cancer, bleeding after intercourse (postcoital bleeding), intermenstrual bleeding, or postmenopausal bleeding may occur. The symptoms of ovarian cancer are nonspecific, and because of this, the diagnosis is often delayed. The most common symptoms include bloating, abdominal fullness (necessitating an increase in clothing size), early fullness after eating, heartburn, and abdominal pain.

Screening and diagnosis: Screening for gynecologic cancers ranges from the Pap smear, which screens for cervical cancer, to visual inspection, and no screening for rarer cancers. The diagnosis of cervical cancer is established by consistent findings on an abnormal Pap smear with a large biopsy of the cervix (conization) performed as an outpatient in the hospital. Stage I cervical cancer is confined to the cervix, Stage II involves spread to the upper two-thirds of the vagina, Stage III involves spread to the lower one-third of the vagina, and Stage IV involves cancer that has spread to the bladder or rectum or outside the pelvis.

No routine screening test exists for cancer of the uterus, but those at high risk can be screened by endometrial sampling and measurement of the endometrial thickness (or lining). Endometrial sampling is an office-based procedure in which a small, flexible plastic catheter is inserted into the uterus, and the cells lining the uterus (endometrial cells) are drawn into the catheter. Endometrial sampling can also serve as the diagnostic test for endometrial cancer. In some cases, if the diagnosis of uterine cancer is in question based on endometrial sampling, a dilation, and curettage (D&C) can be performed as an outpatient procedure in which more extensive sampling of the uterine cavity can be performed. Measurement of endometrial thickness is also an office-based procedure, but in some cases, it is done by a radiologist. Using an ultrasound probe through the vagina (transvaginal ultrasound), the thickness of the lining of the uterus is measured. Stage I cancer is limited to the uterus, Stage II involves extension from the body of the uterus to the cervix, Stage III occurs when the tumor protrudes through the uterus or metastasizes to the vagina, pelvis, or lymph nodes adjacent to the aorta, and Stage IV cancer exists when metastases involve the bladder, the bowel, or organs outside the pelvis in the abdomen.

Other than an annual well-woman examination with palpation of the ovaries, no specific screening is recommended for ovarian cancer. However, for women at high risk or those specifically concerned about ovarian cancer, a transvaginal ultrasonogram (in which the volume of the ovaries is determined), combined with a cancer (CA) 125 blood test, can be performed. The diagnosis of ovarian cancer is made at the time of surgery, although abdominal ultrasonography and computed (CT) scans of the pelvis generally are obtained first. Ovarian cancer is staged as follows: Stage I involves a tumor limited to one or both ovaries, Stage II ovarian cancer exists when the tumor has extended to the pelvis, Stage III cancer involves a tumor outside the pelvis, and Stage IV cancer is characterized by distant metastases (lungs or liver).

For cancer of the vulva, no screening is recommended other than visual inspection during an annual well-woman examination. The diagnosis is made by biopsy of any suspicious lesion. Stage I cancer is less than 2 centimeters (cm) in diameter and confined to the vulva, Stage II cancer is greater than 2 cm in diameter and confined to the vulva, Stage III cancer extends to the anus or urethra or lymph nodes on one side, and Stage IV involves spread to the bladder, rectum, bones of the pelvis, or lymph nodes on both sides.

Screening for vaginal cancer should be performed in the context of the annual well-woman examination. Stage 0 vaginal cancer is referred to as carcinoma in situ, referring to cancer that is localized without apparent spread. Stage I vaginal cancer is limited to the vaginal wall. Stage II vaginal cancer has extended to the subvaginal tissues but not to the pelvic wall. Stage III vaginal cancer involves the pelvic wall. Stage IV vaginal cancer has spread beyond the pelvis or has extended to the bladder or rectum.

No screening exists for cancer of the Fallopian tube. Stage 0 is cancer limited to the lining of the Fallopian tube. Stage I is cancer limited to one tube with extension into the muscular layer of the tube but not to the external surface of the tube. Stage II cancer involves one or both tubes with extension beyond the Fallopian tube. Stage III cancer involves one or both tubes with spread beyond the pelvic cavity. Stage IV cancer involves one or both Fallopian tubes with distant metastases, for example, the lungs.

Specific screening is not recommended for gestational trophoblastic disease. With the advent of obstetric ultrasonography, few cases of gestational trophoblastic disease are diagnosed in advanced stages when symptoms occur. A blood test showing elevated levels of beta-human chorionic gonadotropin (β-HCG) during pregnancy and an ultrasound revealing no fetus is indicative of the disease. Gestational trophoblastic disease is staged as follows—Stage I is limited to the uterus, Stage II involves the female reproductive tract, Stage III has spread to the lungs, and Stage IV has spread elsewhere.

Treatment and therapy: Most gynecologic cancers are treated first with surgery and then by radiation therapy or chemotherapy. However, uterine cancer is treated primarily by surgery. Cervical cancer and cancer of the vulva are treated by surgery with or without radiation therapy. Cancer of the vagina is treated by surgery or radiation, or a combination of the two, depending on the type of tumor. Ovarian cancer is treated by surgery with chemotherapy, and cancer of the Fallopian tube is treated by surgery, with or without chemotherapy. Gestational trophoblastic disease is treated by evacuation of the uterus with chemotherapy.

Prognosis, prevention, and outcomes: Gynecologic cancers range from cancers with excellent prognoses, such as low-risk gestational trophoblastic disease, to those with less favorable prognoses, such as ovarian cancer, which is usually detected in an advanced state. The prognosis of gestational trophoblastic disease is based on the woman’s age, pregnancy history, β-HCG level, tumor size, metastases, and response to chemotherapy. For those at low risk, the cure rate is 100 percent. For those at high risk, the cure rate is 75 percent.

Prognostic factors for uterine cancer include the woman’s age at the time of diagnosis, race, tumor stage, type of tumor, size of the uterus at the time of diagnosis, depth of invasion of the tumor into the layer of uterine muscle, presence of tumor in the blood vessels supplying the uterus, and spread of the tumor outside the uterus to other organs or lymph nodes. The overall five-year survival rates for cancer of the uterus are 87, 72, 51, and 9 percent for stages I, II, III, and IV, respectively.

The prognosis for cervical cancer depends on tumor stage, size of tumor, depth of invasion, and lymph node spread. The availability of a vaccine against HPV has provided a means for the prevention of cervical cancer. Five-year survival rates for Stages I to IV are 80 to 95, 64, 38, and 14 percent, respectively.

Prognosis of cancer of the vulva is related to the tumor stage, size of the lesion, and lymph node involvement. Five-year survival rates for Stages I to IV are 71, 61, 44, and 8 percent, respectively.

The prognosis for vaginal cancer is directly related to the stage at the time of diagnosis. The five-year survival rates for Stages I to IV are 68, 54. 35, and 20 percent, respectively. The overall five-year survival for cancer of the vagina is approximately 45 percent.

The five-year survival rate for all stages of Fallopian tube cancer combined is approximately 40 to 50 percent. Women with Stage I Fallopian tube cancer have five-year survival rates of 65 percent, Stage II disease is 50 to 60 percent, and Stages III and IV are 10 to 20 percent.

The prognosis of ovarian cancer is related to the tumor stage and the amount of residual tumor after surgery. Because most patients are diagnosed in advanced stages, the five-year survival rate is approximately 50 percent.

Bibliography

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Frumovitz, Michael, et al. Diagnosis and Treatment of Rare Gynecologic Cancers. Elsevier, 2023. 

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