What Is Uterine Cancer?

To understand what is uterine cancer, let us start first by understanding the term “cancer”.  Cancer is a disease in the human body wherein, the cells divide uncontrollably and can even pass to other parts of body through blood after invading the local tissues from its point of origin. The cancer that develops in the inner lining of uterus (endometrium), also known as womb where the baby develops and grows is known as uterine cancer or endometrial cancer.

The basic knowledge and importance of uterine cancer is utmost important as this cancer is most prevalent in women that is going through menopause and risk increases with passing age ¹. 

This cancer, is aggravated by various confounding factors that could be a part of lifestyle such as diet, physical activity, alcohol, smoking and hormonal pills. 

Overview

Uterine cancer, or endometrial cancer, is one of the major cancers that prevails in postmenopausal people assigned female at birth (AFAB), usually in those above the age of 55. This cancer has been linked with women who experience postmenopausal bleeding and those undergoing hormonal replacement therapy with pills that only contain oestrogen hormones. Ostrogen is the main hormone responsible for this pathology, with increased levels causing major changes in the tissues of the uterus. Individuals with metabolic syndrome, which encompasses diseases such as diabetes mellitus and obesity, have a higher risk of developing uterine cancer. Regulation over a patient’s diet,  accompanied by physical exercise, is been recommended for high-risk groups. The signs and symptoms of this cancer include unexplained blood loss and abnormal vaginal discharge. The mortality rate from uterine cancer had risen significantly in the last decade. As a result, medical organisations, such as the National Cancer Institute and Cancer Research UK, are carrying out screenings and conducting research to discover prognostic markers that could help in the reduction of uterine cancer before its onset and improve the overall survival of the affected individuals.¹

Causes of uterine cancer

The underlying cause of uterine cancer are genetic mutations that occur in DNA during its replication and repair. These mutations are found in the DNA of cells that form the endometrium (the lining of the uterus), resulting in endometrial hyperplasia, followed by dysplasia and eventually, cancer. These mutations can occur due to excessive exposure to oestrogen hormones. Oestrogen levels are governed by intrinsic and extrinsic factors. Intrinsic factors can include disorders like obesity and diabetes mellitus that disrupt the normal regulation of androgens released by adipose tissue. As androgens are then converted to oestrogen, an imbalance in androgen production also causes dysregulation of oestrogen levels. Hence, disruptions to a person’s metabolism can increase the chance that uterine cancer develops. 

The main extrinsic factor that can heighten the risk of uterine cancer is oestrogen-only hormonal replacement therapy. External intake of oestrogen leads to higher exposure to the hormone in the endometrium, causing atrophic changes to the endometrial lining, which can later lead to cancer. 

There are two types of endometrial cancer:

Type I - cancer caused by an imbalance in oestrogen levels

Type II- cancer caused by factors not related to oestrogen

The underlying genetic mutations for Type I cancers are kRas, PTEN, and microsatellite instability. For Type II cancers it is p53 and HER2/neu mutations. These mutations are important markers detected in genetic testing as the presence of a specific one determines the course of therapeutics and predicts the prognosis. Type II cancer has a poorer prognosis.²   

Signs and symptoms of uterine cancer

The major sign of uterine cance is postmenopausal bleeding (PMB). In a clinical study conducted with 34,432 patients with uterine cancer, PMB was observed in 91% of them. In premenopausal women, irregular menstrual cycles and episodes of intermenstrual bleeding can be observed. 

Other symptoms that patients can present with are pelvic discomfort, nausea and dysuria (painful or burning sensation during urination). When the cancer has spread to other parts of the body (metastasis), changes in bowel and bladder habits and unexplained weight loss can occur. 

A gynaecologist  conducts various physical examinations before undertaking confirmatory diagnostic tests. On physical examination, patients can appear pale due to anemia and a low platelet count that has developed as a result of continuous bleeding over the course of the disease. Upon examination of the abdominal region, the uterus may appear large and tender due to cancerous changes. Lastly, upon vaginal examination, active bleeding or blood clots may appear in the vaginal canal. ³ 

Management and treatment for uterine cancer

The management and treatment of the cancer patient is planned according to the  stages of cancer and tissue changes that predict the course of the disease. If an increase in cell size and uterus enlargement (hyperplasia) is observed in a patient but is not accompanied by morphological changes to the cells (atypia), there are fewer chances that the cells will become cancerous. 

progesterone-based pills, which are known as progestins, are the first-line treatment for uterine cancer. They act bystimulating the thinning of the endometrium. 

For patients with stage I cancer, surgical procedures, such as transabdominal hysterectomy with bilateral salpingo-oophorectomy, are considered the treatment of choice. In these procedrues, the uterus, cervix and adnexa are removed. However, if the patient wishes to maintain reproductive function, then progestins can be continued without surgical intervention if approved by the gynaecoloigist’s evaluation. 

Stage II patients - hysterectomy and adjuvant radiotherapy is recommended

Stage III patients - transabdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic radiation therapy are considered as treatments of choice

Stage IV patients - cancer removal surgery followed by palliative care to improve the quality of life 

FAQs

How is uterine cancer diagnosed?

Followed by physical examination, uterine cancer is diagnosed with the help of transvaginal ultrasound. If the thickness of the endometrium exceeds the normal range of 4mm, endometrial biopsy has to be considered. However, transvaginal ultrasound fails to be sensitive in premenopausal people AFAB, owing to high variations in endometrial thickness that occur during the menstrual cycle. Due to this, endometrial biopsy is considered the main diagnostic method for premenopausal people AFAB. 

For people AFAB who are at low risk of developing uterine cancer, a less invasive diagnostic check is performed, known as pipelle biopsy. It is conducted by inserting a small tube, a pipelle, into the cervix to extract a sample ofendometrial tissue for histopathological investigation. Examination of the tissue under a microscope can showvariation in cell size morphology that can be indicative of cancer.⁴ 

What are the stages of uterine cancer?

There are four stages of uterine cancer outlined by the International Federation of Gynecology and Obstetrics:⁵

Stage I - cancerous growth is found within uterus

Stage II - cancer manifests in the uterus and invades thecervix

Stage III - cancer invasion of the uterus, cervix, ovaries, fallopian tubes, and vagina. Involvement of lymph nodes can occurStage IV - cancer metastasises, or spreads, to other organs, such as the bladder and therectum. Cancer can invade tissues beyond the pelvis⁵ 

How can I prevent uterine cancer?

Uterine cancer can be prevented by consulting a gynecologist regarding the use of oestrogen-only hormonal replacement therapy, especially after menopause.It is recommended to instead take combination pills that contain both oestrogen and progesterone hormones. Moreover, birth control pills have been shown to reduce the risk of cancer, however,  it bears their own side effects and is not recommended unless prescribed by specialists.  Lifestyle changes, like weight management, physical exercise and reduction in consumption of tobacco and alcohol is highly recommended. 

Who is at risk of uterine cancer?

The major cause of uterine cancer is the excessive release of oestrogen that causes an increase in the thickness of the endometrial lining. Hormonal replacement therapy with oestrogen-only pills postmenopause can predispose an individual to uterine cancer. Hence, it is always advisable to consult your GP before initiating hormonal therapy  and to take oestrogen supplements in conjunction with progesterone. In addition, an imbalance in oestrogen levels can be caused by irregular or an increased number of ovulation cycles. This similalry leads to infertility, early first period, late menopause, and polycystic ovarian syndrome.

Excessive fat deposition leads to conversion of male hormones, such as androgens, to female hormones, like oestrogen and progesterone. Hence, obesity, metabolic syndrome and diabetes mellitus are major risk factors of uterine cancer.

Tamoxifen, a drug that is prescribed to breast cancer patients to reduce the levels of ostrogens reaching breast cells has the opposite effect in the uterus, causing exposure to high oestrogen levels. Thus, usage of this drug can also increase the chances of  developing uterine cancer. 

A rare type of syndrome, known as Lynch syndrome, that causes colon cancer has also been associated with increasing the risk that a person develops uterine cancer. 

When should I see a doctor?

The National Institute for Health and Care Excellence (NICE) states that if postmenopausal bleeding prevails for more than 2 months, then one must be referred to urgent cancer care. Moreover, unexplained vaginal discharge, hematuria ( blood in urine), irregular menstual periods, unexplained weight loss and pain in the pelvic region are some of the major signs that one should look out for and consult adoctor as soon as possible if they occur.

Summary

Uterine cancer, or endometrial cancer, is charcterised by abnormal growth of cells that make up the uterine lining. The cancer arises as a result of specific mutations accumulating in the cells of the uterus. Excess levels of oestrogen hormones in the body drives the progression of cancer. Uterine cancer can be lethal if not detected early. Physical examination and diagnostic testing, like histopathology and genetic testing, are needed to confirm the diagnosis. Treatment can involve medications or surgical interventions, depending on the stage of the cancer. Hence, it is important for people AFAB to be aware of the signs and symptoms of uterine cancer so that they can seek appropriate medical help as soon as possible.

References

1. Faizan U, Muppidi V. Uterine Cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Feb 1]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK562313/. 
2. Njoku K, Barr CE, Crosbie EJ. Current and Emerging Prognostic Biomarkers in Endometrial Cancer. Frontiers in Oncology. 2022 Apr 22;12. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.890908/full ‌
3. Boeckstaens S, Dewalheyns S, Heremans R, Vikram R, Timmerman D, Van den Bosch T, et al. Signs and symptoms associated with uterine cancer in pre- and postmenopausal women. Heliyon. 2020 Nov;6(11):e05372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649270/ 
4. Koutlaki N, Dimitraki M, Zervoudis S, Skafida P, Nikas I, Mandratzi J, et al. Hysteroscopy and endometrial cancer. Diagnosis and influence on prognosis. Gynecological Surgery. 2010 Jul 28;7(4):335–41. https://gynecolsurg.springeropen.com/articles/10.1007/s10397-010-0613-0 
5. Kim HS, Song YS. International Federation of Gynecology and Obstetrics (FIGO) staging system revised: what should be considered critically for gynecologic cancer? Journal of Gynecologic Oncology. 2009;20(3):135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757555/ 
6. Felix AS, Brinton LA. Cancer Progress and Priorities: Uterine Cancer. Cancer Epidemiology Biomarkers & Prevention. 2018 Sep;27(9):985–94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504985/

This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Kanisha Mehta

Master of Science in Biomedical Sciences (Immunology) at the University of Westminster, Bachelor of Dental Surgery (BDS), Saurashtra University, India

I am Kanisha, a graduate biomedical researcher and a former dentist. As a health professional, I have read, written, heard, and seen many stories of patients going through an array of ailments such as oral diseases, cancers, and nutritional deficiencies and I consider it a moral duty to spread awareness regarding this ailment which starts off small and turns up taking a bigger picture. I hope with this piece of article you could make the right choice of steps needed to be taken for prevention and cure.

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