About Gynecologic Cancer

Gynecologic cancers affect the female reproductive system, including:

• Ovarian cancer
• Uterine (endometrial) cancer
• Vaginal cancer
• Cervical cancer
• Vulvar cancer

Statistics:

In 2022, gynecologic cancers accounted for 14,73,427 new cases and 6,80,372 deaths globally, with significant regional disparities in incidence and mortality rates. The highest rates were observed in Eastern Africa and countries with very high and low HDI, with Eswatini recording the most severe statistics. If current trends continue, the number of new cases and deaths from gynaecological cancers is expected to rise over the next two decades, highlighting the urgent need for effective interventions.

How to Recognize Symptoms?

Symptoms vary by cancer type but common signs across gynecologic cancers include:

• Abnormal vaginal bleeding
• Vaginal discharge
• Pelvic pain
• Difficulty urinating

Symptoms by Cancer Type

Ovarian Cancer

• Bloating or swelling in the abdomen
• Frequent urination
• Pelvic or back pain
• Loss of appetite or feeling full quickly
• Changes in bowel habits
• Fatigue
• Unexplained weight loss

Endometrial (Uterine) Cancer

• Bleeding after menopause
• Heavy or irregular menstrual bleeding
• Vaginal discharge
• Difficulty urinating
• Pelvic pain

Vaginal Cancer

• Abnormal vaginal bleeding
• Vaginal discharge
• Pelvic pain
• Painful and frequent urination

Cervical Cancer

• Abdominal pain
• Foul-smelling vaginal discharge
• Pelvic or back pain
• Spotting between periods or after intercourse
• Bleeding after menopause

Vulvar Cancer

• Persistent itching in the vulva
• Vulvar bleeding
• Pain, soreness, or tenderness in the vulva
• Burning sensation while urinating
• Visible wart-like growth or sore on the vulva

Types of Gynecologic Cancer

1) Ovarian Cancer / Primary Peritoneal Cancer

• Overview: Seventh most common gynecologic cancer worldwide.
• Subtypes:
  • Epithelial ovarian cancer: Most common; starts in the cells covering the ovary.
  • Fallopian tube cancer: Starts in the fallopian tubes; considered epithelial ovarian cancer.
  • Primary peritoneal cancer (PPC): Rare; starts in the lining of the abdomen (peritoneum); type of epithelial ovarian cancer.
  • Germ cell ovarian tumors: Originate from egg-producing cells; can be benign or malignant.
  • Sex cord stromal tumors: Originate from hormone-producing ovarian cells; can be benign or malignant. Granulosa cell tumors are the most common.
  • Borderline ovarian tumors: Abnormal but not cancerous; usually cured with surgery.

2) Endometrial Cancer / Uterine Cancer / Gestational Trophoblastic Disease (GTD)

• Cancer of the uterine lining (endometrium).
• The uterus is where pregnancy occurs; fallopian tubes and ovaries are located nearby.
• The cervix connects the uterus to the vagina.

3) Vaginal Cancer

• Begins in the vagina (birth canal).
• Most commonly affects the lining (squamous epithelium) of the vagina.
• Usually occurs in people aged 50–70 years.

4) Cervical Cancer

• Starts in the cervix — the lower part of the uterus opening into the vagina.
• Almost always caused by persistent infection with Human Papillomavirus (HPV).
• HPV integrates into cervical cell DNA, causing abnormal cell growth.

5) Vulvar Cancer

• Starts in the vulva — the external female genitalia (labia, clitoris, urethra opening, vaginal opening, and surrounding skin).
• Rare cancer, associated with:
  • Smoking
  • HPV infection
  • Chronic irritation or inflammation of the vulva

Gynecologic Cancer Risk Factors

• Family history: Breast, ovarian, uterine, or colon cancer; especially with BRCA1/BRCA2 mutations.
• Age: Risk increases with age.
• Reproductive history: Not having children, late childbearing, or infertility increase risk, especially for ovarian cancer.
• Hormonal factors: Estrogen-only hormone replacement therapy (HRT) after menopause increases uterine cancer risk.
• Genetic mutations: BRCA1 and BRCA2 gene mutations significantly raise cancer risk.
• Obesity: Linked to higher risk, particularly uterine cancer.
• Smoking: Raises risk, especially for vulvar cancer.
• Exposure to diethylstilbestrol (DES): A synthetic estrogen linked to rare vaginal and cervical cancers.
• Infections: Persistent HPV infection is the main risk for cervical cancer.

Causes of Gynecologic Cancers

1) Cervical Cancer

• How it begins: Cervical cancer starts when normal cervical cells acquire changes (mutations) in their DNA that cause them to grow uncontrollably and avoid normal cell death. This results in too many cells forming tumors that can invade nearby tissues and spread.
• Main cause: Persistent infection with Human Papillomavirus (HPV), a common sexually transmitted virus. While many people clear HPV naturally without issues, in some cases HPV causes DNA changes in cervical cells leading to cancer.

2)Endometrial Cancer (Uterine Cancer)

• Exact cause: Not fully understood.
• What is known: Changes occur in the cells lining the uterus (endometrium) that transform normal cells into cancer cells.
• Key factors:
  • Most cancer cells have estrogen and/or progesterone receptors. Hormonal interactions stimulate abnormal growth.
  • Hormonal imbalance—especially excess estrogen relative to progesterone—can drive excessive growth of the uterine lining and cancer development.
  • Risk factors: Obesity, hormone imbalance, and genetics affect hormone levels and thus cancer risk.
• Genetics: Researchers are learning about specific gene mutations that cause endometrial cells to become cancerous.

3) Ovarian Cancer

• Exact cause: Unknown for most cases.
• New insights: Ovarian cancer likely begins in cells at the end of the fallopian tubes, not just in the ovaries. This opens new paths for research on prevention and early detection.
• Theories based on risk factors:
  • Ovulation theory: Pregnancy and birth control pills reduce ovulation and lower ovarian cancer risk, suggesting frequent ovulation might increase risk.
  • Tubal ligation/hysterectomy effect: These procedures reduce risk possibly by blocking cancer-causing agents that enter through the vagina, uterus, and fallopian tubes to reach ovaries.
  • Hormonal theory: Male hormones (androgens) might contribute to ovarian cancer development.
• Genetic causes:
  • Inherited mutations: BRCA1 and BRCA2 gene mutations significantly increase risk. Other inherited cancer syndromes include mutations in PTEN, STK11, MUTYH, and mismatch repair genes (MLH1, MSH2, MSH6, PMS1, PMS2). Genetic counseling and testing are recommended for those with family histories of related cancers.
  • Acquired mutations: Most ovarian cancers involve DNA mutations acquired during life (not inherited). These mutations may include changes in genes like TP53 and HER2, which may affect prognosis.
• No specific environmental or dietary chemicals have been conclusively linked to causing ovarian cancer mutations.

Risk Factors for Gynecologic Cancers

Cervical Cancer

• Persistent HPV infection (almost all cases)
• Age: Usually affects women aged 30–50, but younger women are at risk too
• Smoking (weakens immune system → persistent HPV infection)

Ovarian Cancer

• Age: Risk increases around menopause
• Family history of ovarian, fallopian tube, primary peritoneal cancer, or premenopausal breast cancer
• Personal history of premenopausal breast cancer
• Infertility and not having children (pregnancy and birth control pills lower risk)
• Family history of colon and endometrial cancers, or male breast cancer in family
• Ashkenazi Jewish heritage

Uterine/Endometrial Cancer

• Taking estrogen alone without progesterone
• Overweight/obesity (not maintaining healthy weight)
• Late menopause (after age 52)
• Diabetes or high blood sugar
• Not bearing children
• High blood pressure (hypertension)
• Family history of endometrial or colon cancer
• Use of tamoxifen (a breast cancer medication)

Vaginal Cancer

• Persistent HPV infection
• Smoking
• Older age (risk increases especially after 60 years)
• Exposure to diethylstilbestrol (DES), a hormone once used in pregnancy

Vulvar Cancer

• Lichen sclerosis (chronic skin condition causing thin, white patches in genital area)
• Persistent HPV infection
• Smoking

Diagnosis of gynecologic cancers

Cervical Cancer (CC)

• Screening:
  • Pap test was the original method but had low sensitivity (~61.1% for detecting precancerous lesions).
  • HPV-DNA testing (since 2002) greatly improved sensitivity (~94.1%).
• Prevention:
  • HPV vaccines (bivalent, quadrivalent, nonavalent) protect against high-risk HPV types responsible for most cervical cancers.
• Global Goal: WHO aims to eliminate cervical cancer by 2030 (reduce incidence below 4 per 100,000 woman-years).
• Note: CC is the only gynecologic cancer with established primary (vaccination) and secondary (screening) prevention.

Endometrial Cancer (EC)

• Signs: Postmenopausal vaginal bleeding (early symptom in 90% cases).
• Screening: No standard population screening method yet.
• Endometrial sampling has variable sensitivity (56–100%).
• Transvaginal ultrasound for endometrial thickness (cutoff ~5mm) has good sensitivity/specificity but hasn’t improved mortality.
• High-risk groups (e.g., Lynch syndrome): Annual gynecologic evaluation and ultrasound starting age 25; prophylactic hysterectomy recommended after childbearing.

Ovarian Cancer (OC)

• Challenge: Most lethal gynecologic cancer with poor 5-year survival (~30%). Diagnosed late in ~2/3 cases.
• Screening:
  • CA-125 blood test and ultrasound have not reduced mortality in general or high-risk populations (BRCA mutations).
  • Prophylactic bilateral salpingo-oophorectomy (removal of ovaries and fallopian tubes) is the only proven risk reduction in BRCA carriers (recommended between 35-40 or after childbearing).

Future Directions in Diagnosis

• Liquid biopsies: Non-invasive tests using blood samples to detect cancer DNA.
• Artificial Intelligence (AI): AI models outperform humans in prediction using medical records, imaging, cytology, and molecular data.
• Combining AI with liquid biopsies may improve early diagnosis and treatment but still requires validation in large populations.

Screening vs Early Diagnosis

• Screening: Testing asymptomatic at-risk women; complex and resource-intensive; measured by sensitivity (>70%) and specificity (>95%).
• Early Diagnosis: Identifying symptomatic women early; involves fewer resources.

Treatment of Gynecologic Cancers

Treatment depends on the type, stage of cancer, and patient health, and often combines several approaches:

Surgery:

Commonly involves hysterectomy (uterus removal), oophorectomy (ovaries removal), lymph node dissection.

Radiation Therapy:

Uses high-energy rays to kill or damage cancer cells; can be primary or adjuvant treatment.

Chemotherapy:

Uses drugs orally or by injection to kill cancer cells; varies by cancer type and stage.

Hormone Therapy:

Blocks or reduces effects of hormones; mainly for hormone-sensitive cancers like endometrial cancer.

Targeted Therapy:

Drugs designed to attack cancer cells specifically without harming normal cells.

Immunotherapy:

Boosts the immune system’s ability to recognize and destroy cancer cells.

Clinical Trials

• Clinical trials offer access to new treatments and help advance knowledge.
• Resources for finding trials:
  • NIH Clinical Research Trials and You
  • National Cancer Institute’s Clinical Trials pages
  • ClinicalTrials.gov

Complementary and Alternative Medicine (CAM)

• Definition:
  • Complementary medicine is used alongside standard cancer treatments.
  • Alternative medicine is used instead of standard treatments.
• Examples: Acupuncture, vitamin/herbal supplements.
• Caution: Many CAM therapies lack scientific proof of safety and effectiveness.
• Advice: Always discuss with your doctor before starting any CAM to understand potential risks and benefits.

FAQs: Most Asked Questions about Gynecologic Cancers

What are the most common gynecologic cancers?

• Uterine cancer: ~60,000 new cases/year (most common)
• Ovarian cancer: ~20,000 new cases/year
• Cervical cancer: ~10,000 new cases/year
• Vulvar & vaginal cancers: ~10,000 combined cases/year (rarest)
• Most cervical, vulvar, and vaginal cancers are related to HPV infection.

What symptoms should women watch for?

• Ovarian cancer: Bloating, Pelvic/abdominal pain, Frequent urination, Difficulty eating/feeling full. If symptoms persist daily for weeks, see a doctor.
• Uterine & cervical cancers: Postmenopausal bleeding or irregular bleeding.
• Vaginal & vulvar cancers: Abnormal bleeding, Lumps or bumps, Non-healing ulcers, Pain during intercourse.

Are diagnostic tests available?

• Cervical cancer: Pap test available.
• Ovarian & uterine cancers: No standard screening; diagnosis mainly symptom-based, except for patients with hereditary risk like Lynch Syndrome who get closer monitoring.

Why see a gynecologic oncologist instead of a regular OB/GYN?

• Better outcomes with specialized surgical skills and treatment plans.
• Gynecologic cancers are complex and require specialized expertise.

When to seek a second opinion?

• If uncomfortable with diagnosis or treatment plan.
• If your doctor dismisses your concerns, trust yourself and seek another opinion.

Who should consider genetic testing?

• Women with family history of breast, pancreatic, or melanoma cancers.
• Those with high-grade ovarian cancer or diagnosed under age 50.
• Patients with uterine cancer due to Lynch Syndrome risk.
• Discuss genetic counseling with your doctor if you fit these categories.

What clinical trials are available?

• Many non-chemotherapy treatments like PARP inhibitors, immunotherapy, and vaccines (especially for HPV-related cancers).
• Trials are testing checkpoint inhibitors and combinations with vaccines to boost immune response.

Any progress in low-grade serous ovarian cancer?

• Targeted therapies like MEK inhibitors are promising.
• Hormonal therapies (letrozole, tamoxifen) also show potential, with mild side effects.

Outlook for recurrent uterine cancer?

• Improved survival from ~12 months to 2-3 years with chemotherapy and clinical trials.
• Molecular targeted therapies offer hope for better outcomes.

New developments in fallopian tube cancer?

• Usually grouped with ovarian/peritoneal cancers in trials.
• Treatments include PARP inhibitors and bevacizumab.

What about cancer and fertility?

• Cancer and its treatments can impact fertility.
• Discuss fertility preservation and options with your care team before starting treatment.