Cervical Cancer Guide | Symptoms, Stages, Screening & Treatment Options
Learn about cervical cancer, including its causes, early symptoms, stages, screening methods like Pap and HPV tests, and modern treatment options such as surgery, radiotherapy, chemotherapy, and immunotherapy.
Cervical Cancer and Human papillomavirus
Cervical cancer is caused by a persistent infection with the human papillomavirus (HPV) in the cervix, which is the lower and narrow part of the uterus.
In most cases, HPV resolves on by itself but in others, it can lead to cell abnormalities that develop into cancer.
Despite predictions that this number will rise globally, the majority of the increase is expected to occur place in low- and middle-income countries (LMICs).
In 36 countries, including those in sub-Saharan Africa, Latin America, and India, cervical cancer is the primary cause of cancer-related fatalities.
Cervical cancer is second leading cancer in India
Cervical cancer is the fourth most prevalent cause of cancer death for women worldwide and the fourth most common type of cancer to be diagnosed.
India was a significant contribution to the global cervical cancer burden in 2020, accounting for almost one-fourth of cervical cancer-related deaths and about one-fifth of new cases.
Cervical cancer ranks second among cancers in India in terms of both incidence (18.3%) and cancer death (18.7%) among females in 2020.
During this time, age-standardized incidence and mortality rates of cervical cancer have decreased in India, following the global trend.
This downward tendency hasn’t been consistent, though, throughout all Indian states.
Reason behind decline trend of cervical cancer in India is-
- Improved literacy rates
- Delayed age at marriage
- First sexual intercourse and first childbirth
- Low parity
- Increased use of contraception
- Improved menstrual hygiene
- Decreased tobacco use among women
How normal cell converted into cervical cancer
Most cervical cancers are caused by long-term infection with particular high-risk forms of human papillomavirus (HPV).
Most women’s cells that are abnormal will gradually go away without treatment.
Some women’s abnormal cells can develop into true (invasive) malignancies. Treatment of abnormal modifications in cervical cells can prevent nearly all cervical malignancies.
HPV infection can result in precancerous modifications called cervical dysplasia. If not discovered and treated, these alterations may eventually lead to cancer.
Steps involved
Cells in the transformation zone do not spontaneously develop into cancer.
Normal cells in the cervix gradually develop abnormal modifications.
Doctors refer to these cell modifications as
- Cervical Intraepithelial Neoplasia (CIN),
- Squamous Intraepithelial Lesion (SIL), and
- Dysplasia.
When abnormal modifications in the cervix are identified, they are graded on a 1–3 scale based on how much of the cervical tissue seems abnormal.
• CIN1, also known as mild dysplasia or low grade SIL, indicates minor abnormal tissue. These cells usually revert to normal cells.
• In CIN2 or CIN3, also known as moderate/severe dysplasia or high-grade SIL, more tissue appears abnormal. With these cell alterations, there is a greater possibility that the cells will develop into cancer cells, which will require strict monitoring or removal.
Understanding the Cervix and Its Role
Cervical cancer originates in the cervix, which is the small opening into the uterus that connects to the vagina via the endocervical canal.
The cervix is divided into the ectocervix and the endocervix.
The ectocervix consists of stratified squamous epithelial cells, whereas the endocervix consists of of simple columnar epithelial cells.
Stratified squamous and columnar epithelium form the squamocolumnar junction in the endocervical canal.
The transformation zone is the region of the cervix where the stratified squamous epithelium of the ectocervix meets the columnar epithelium of the endocervical canal, and it is characterized by squamous metaplasia in which the columnar epithelium is replaced by metaplastic squamous epithelium.
This transformation zone is the most likely site for the development of cervical cancer because it is a major site of premalignant transformation caused by persistent HPV infection.
There are two major histological subtypes of cervical cancer:
- Squamous cell carcinoma (SCC) and
- Adenocarcinoma
Causes and Risk Factors
- Persistent infection with high-risk human papillomavirus (HPV) types, particularly HPV-16 and HPV-18
- Early onset of sexual activity or having multiple sexual partners, which increases the risk of HPV exposure
- Cigarette smoking
- A weakened immune system (such as from HIV infection or immunosuppressive therapy)
- Long-term use of oral contraceptives
Warning Signs and Symptoms
- Abnormal vaginal bleeding, such as bleeding between periods, after sexual intercourse, or after menopause
- Unusual vaginal discharge that may be watery, bloody, or foul-smelling
- Pelvic pain or pain during sexual intercourse
- Leg pain and swelling (as the tumor can press on nerves)
Types of cervical cancer
Cervical cancers and cervical precancers are distinguished by their appearance in the lab under a microscope. The two main kinds of cervical cancer are squamous cell carcinoma and adenocarcinoma.
Squamous cell carcinomas
Squamous cell carcinoma is the most common type of cervical cancer, accounting for about 70–80% of all cases.
It develops from the squamous cells that line the exocervix and most often begins in the transformation zone, the area where the exocervix meets the endocervix.
Adenocarcinomas
Adenocarcinoma is the second most common type of cervical cancer.
It arises from glandular cells, specifically the mucus-producing cells of the endocervix.
These cancers account for most of the remaining cervical cancer cases after squamous cell carcinoma.
Both squamous cell carcinomas and adenocarcinomas
Less commonly, cervical cancers display characteristics of both squamous cell carcinoma and adenocarcinoma.
These are known as adenosquamous carcinomas, or mixed carcinomas.
Stages of Cervical Cancer
Cancer staging describes how far the disease has progressed in the body, including whether it has spread beyond its original site to nearby or distant areas. Determining the stage of cervical cancer is crucial for planning the most effective treatment.
The International Federation of Gynecology and Obstetrics (FIGO staging system) is an internationally accepted framework used by doctors to describe the stage of gynecological cancers, including cervical cancer.
Stage 0 (Carcinoma in situ)
At this stage, abnormal or precancerous cells are present only on the surface layer of the cervix. The cancer has not invaded deeper cervical tissue.
Stage I cervical cancer
At this stage, the tumor is confined to the cervix.
- Stage IA: The tumor is so small that it can only be seen under a microscope.
- Stage IB: The tumor is visible without a microscope but is still contained within the cervix.
Stage I is further divided into IA and IB, depending on the size and depth of invasion of the tumor.
Stage IA is subdivided based on the deepest point of tumor invasion.
Stage 1A1: The deepest point of tumor invasion is 3 mm or less.
Stage 1A2: The deepest point of tumor invasion is more than 3 mm but not more than 5 mm.
Stage IB is further subdivided based on tumor size and depth of invasion:
Stage IB1: Tumor is 2 cm or smaller, with a depth of invasion greater than 5 mm.
Stage IB2: Tumor is larger than 2 cm but not larger than 4 cm.
Stage IB3: Tumor is larger than 4 cm.
Stage II cervical cancer
At this stage, the cancer has extended beyond the cervix into surrounding tissues but has not reached the pelvic wall.
In Stage II, the cancer may have spread to:
- The upper two-thirds of the vagina OR
- The tissues surrounding the uterus (parametrium)
Stage II is subdivided based on how far the cancer has spread:
- Stage IIA: Cancer has spread from the cervix to the upper two-thirds of the vagina but has not invaded the tissues around the uterus (parametrium).
- Stage IIA1: Tumor is 4 cm or smaller.
- Stage IIA2: Tumor is larger than 4 cm.
- Stage IIB: Cancer has spread from the cervix into the tissues surrounding the uterus (parametrium).
Stage III cervical cancer
At this stage, the cancer has progressed further and may involve:
- The pelvic wall or the lower part of the vagina
- Nearby lymph nodes
- Ureter obstruction, which can cause urine to back up into the kidneys
Stage III indicates more advanced local spread but has not yet reached distant organs.
Stage III is subdivided based on the extent of cancer spread:
- Stage IIIA: Cancer has spread to the lower third of the vagina but has not reached the pelvic wall.
- Stage IIIB: Cancer has spread to the pelvic wall, and/or the tumor is large enough to block one or both ureters, potentially causing kidney swelling or impaired function.
- Stage IIIC: Cancer has spread to the lymph nodes.
- Stage IIIC1: Cancer involves pelvic lymph nodes.
- Stage IIIC2: Cancer involves para-aortic lymph nodes.
Stage IV cervical cancer
This is the most advanced stage of cervical cancer.
The cancer has spread to neighboring organs, including the bladder and colon.
The cancer has spread to distant organs beyond the cervix, including the lungs, liver, and bone.
Stage IV cervical cancer has spread beyond the pelvis to the bladder, rectum, or other areas of the body.
Stage IV is subdivided into stages IVA and IVB, based on where the cancer has spread.
- Stage IVA: Cancer has spread to nearby pelvic organs, such as the bladder or rectum.
- Stage IVB: Cancer has spread to distant parts of the body, including the liver, lungs, bones, or distant lymph nodes.
Stage IV is also called metastatic cancer.
Recurrent cervical cancer
Recurrent cervical cancer is cancer that has returned after treatment. The cancer may return in the cervix or as metastatic cancers in other parts of the body.
Read more about breast cancer….
Breast Cancer: How to Recognize Early Signs & Get Treatment
Diagnosis and Screening Methods
Early-stage cervical cancer often does not cause noticeable symptoms and may be detected during routine screening or a pelvic examination.
1. Pelvic Examination:
A pelvic exam is performed in patients presenting with symptoms of cervical cancer or as part of routine gynecological care.
2. Pap Smear Test:
A Pap smear helps identify abnormal cervical cells.
- High-grade precancerous lesions (HSIL) or recurrent low-grade lesions (LSIL) on a Pap smear may indicate the need for further evaluation.
3. Colposcopy and Biopsy:
- Colposcopy provides a magnified view of the cervix to examine any abnormal areas.
- Suspicious lesions are biopsied for definitive diagnosis.
- If a precancerous lesion is confirmed, a large loop excision of the transformation zone (LLETZ) is performed to remove abnormal cells and prevent progression to cancer.
Pap Smear and HPV Testing
Pap Smear Test
A Pap test is a screening procedure used to detect abnormal cells on the cervix, the lower part of the uterus that opens into the vagina. If abnormal cervical cells are not identified and treated, they can progress to cervical cancer.
During the test, a doctor or nurse inserts a speculum into the vagina to view the cervix.
Cells are collected from the surface of the cervix using a soft brush or special stick.
The collected cells are sent to a laboratory for analysis to check for abnormalities.
HPV Test
An HPV test detects the presence of human papillomavirus (HPV) DNA in cells collected from the cervix.
HPV is a sexually transmitted infection (STI) that usually clears on its own in most people. However, persistent infection with high-risk HPV types can cause abnormal cervical cells, which may progress to cervical cancer if left untreated.
Certain types of HPV are more likely to cause cervical cancer.
The HPV test can tell your doctor if you have HPV and which type it is.
A doctor or nurse inserts a speculum into the vagina to view the cervix.
Cells are collected from the surface of the cervix using a soft brush.
The collected cells are sent to a laboratory to test for the presence of HPV DNA.
Co-testing
When Pap tests and HPV tests can be done at the same time.
Treatment Options
Surgery
Surgery is an effective method of treating certain early-stage cancers since it includes the actual removal of cancerous tissue. It can also be useful to remove metastatic tissue.
The types of surgery used to treat cervical cancer include
- Total hysterectomy
- Radical hysterectomy
- Radical hysterectomy
- loop electrosurgical excision procedure (LEEP)
- Conization
- Radical trachelectomy
Total hysterectomy
Total hysterectomy, with or without salpingo-oophorectomy (the removal of one or both ovaries), is still the most popular therapy for women who have finished their reproductive lives.
Radical hysterectomy
Radical hysterectomy is most usually utilized for large cervical cancer tumors (up to 4 cm in size). It involves full removal of the uterus, cervix, parametria, and upper vaginal cuff.
Loop Electrosurgical Excision Procedure (LEEP)
The Laparoscopic Approach to Cervical Cancer (LACC) trial found that performing radical hysterectomy using laparoscopy was associated with a higher risk of cancer recurrence, potential loss of fertility, and long-term urinary dysfunction.
LEEP uses a thin wire loop to remove abnormal tissue from the cervix.
- The procedure can be performed under local anesthesia.
- It is suitable for low-cost clinical settings and effectively treats precancerous cervical lesions.
Conization
Conization is a procedure that removes a cone-shaped wedge from the cervix, including the transformation zone and either all or a portion of the endocervical canal.
It requiring hospitalization and incurring much higher expenditures.
Radical trachelectomy
Radical trachelectomy is the removal of the cervix, surrounding tissue (parametrium), and upper vagina using vaginal, laparoscopic, or robot-assisted procedures.
The choice of surgical treatment is heavily influenced by the disease stage and extent of spread.
Women of childbearing age with early-stage disease require a more conservative treatment approach, with fertility-sparing operations such as LEEP, conization, and trachelectomy.
Radiotherapy
Radiotherapy uses high energy x-rays and is a major treatment in the management of cervical cancer.
The three types of radiation therapy currently used to treat cervical cancer are
- External beam radiation therapy (EBRT),
- Intensity-modulated radiotherapy (IMRT), and
- Brachytherapy (internal RT).
EBRT:
- EBRT directs high-energy radiation beams from outside the body into the tumor.
- It is the most commonly used form of radiotherapy for treating cancer.
IMRT:
- IMRT is an advanced form of radiotherapy that shapes photon or proton radiation beams to match the tumor’s contours.
- It helps spare surrounding healthy tissues and can be used for both cancerous and non-cancerous tumors.
Brachytherapy:
- Like IMRT, brachytherapy minimizes radiation exposure to nearby tissues.
- It involves either delivering a high dose of radiation directly to the tumor or placing a radioactive implant at the tumor site.
Adverse effects associated radiotherapy
- Diarrhoea
- Abdominal cramps
- Pelvic pain
- Skin toxicity
- Lymphedema
- Sexual dysfunction
While there is a complete response in 68.3% of patients with stage IIA-IIIB cervical cancer.
20–50% of women, radiotherapy alone fails to control the progression of locally advanced disease.
To improve the efficacy of radiotherapy, it is frequently combined with chemotherapy, particularly for bigger cervical cancer lesions.
Chemotherapy
Chemotherapy is an essential component of the conventional cervical cancer treatment regimen, and it is often used as an adjuvant therapy after surgery when poor prognostic tumor characteristics increase the possibility of returning disease.
Cisplatin, a platinum-based chemotherapy drug, is the most effective single agent for treating cervical cancer.
Despite the initial patient response to cisplatin, increasing resistance during the course of treatment is frequently recorded, reducing the efficacy of additional second-line platinum-based chemotherapies.
Some research showed that
Cisplatin alone has a response rate of approximately 20%.
When combined with topotecan, the response rate increases to around 39%.
Similar improvements in response rates have been observed when cisplatin is combined with paclitaxel.
Currently, topotecan, paclitaxel and other non-platinum-based chemotherapeutics such as 5-fluorouracil and bleomycin, are therefore commonly used in combination with cisplatin for treating cervical cancer.
Future outlook on cervical cancer therapies
Immunotherapy
Advantages:
- Specifically targets dysplastic, precancerous, and malignant cervical epithelial cells that express HPV oncoproteins.
- Minimizes damage to normal, healthy tissues.
Living With and Beyond Cervical Cancer
Living with and after cervical cancer necessitates a holistic approach to long-term health and well-being, with an emphasis on managing physical and emotional side effects of therapy, the fear of recurrence, and significant financial constraints.
To improve long-term quality of life, it is necessary to maintain medical monitoring, support networks, and access to services such as support groups, nutritional counseling, and complementary therapy.
- Monitoring: After treatment is completed, regular check-ups and monitoring are required to monitor for recurrence and manage any late-onset treatment side effects, such as fatigue, persistent pain, or other health difficulties.
- Treatment Side Effects: Survivors of chemotherapy and radiation may experience long-term symptoms including as tiredness, dry mouth, and other physical difficulties.
- Fear of recurrence of disease: Fear of recurrence is a common issue, and survivors may experience anxiety, sadness, or post-traumatic stress disorder.
- Lifestyle and Well-being: Survivors are encouraged to take part in activities that improve overall health, such as light exercise, meditation, and stress-reduction techniques.
Where to Find Support and Resources
- Healthcare Providers
- Mental Health Professionals
Prevention and HPV Vaccination
There are two types of HPV vaccines, bivalent and quadrivalent; both are licensed and available in India.
The HPV vaccine protects against the types of HPV that most often cause cervical, vaginal, and vulvar cancers.
- HPV vaccination is recommended for preteens aged 11 to 12 years, but can be given starting at age 9.
- HPV vaccination also is recommended for everyone through age 26 years, if they are not vaccinated already.
- HPV vaccination is not recommended for everyone older than age 26 years. However, some adults age 27 through 45 years who are not already vaccinated may decide to get the HPV vaccine after speaking with their doctor about their risk for new HPV infections and the possible benefits of vaccination. HPV vaccination in this age range provides less benefit, as more people have already been exposed to HPV.
If vaccination is started before age 15, a two-dose schedule is recommended, with the doses given 6 to 12 months apart. For people who start the series after their 15th birthday, the vaccine is given in a series of three shots.
Conclusion: Awareness and Early Detection Save Lives
Regular screening tests such as the Pap smear and HPV test can detect precancerous cells and high-risk Human Papillomavirus (HPV) strains before they develop into cancer.
Early discovery considerably improves the prognosis, with a five-year survival rate of more than 90% if discovered early.
Awareness also supports preventative measures such as HPV vaccination and a healthy lifestyle, resulting in a more comprehensive approach to disease control.
Raising awareness allows women to better understand the risk factors, symptoms, and preventive strategies for cervical cancer.
It encourages women to receive the HPV vaccine, which protects against the virus strains that cause the majority of cervical malignancies.
Vaccinate against HPV to protect yourself from the virus that causes the majority of cervical malignancies.
To lower the risk of cancer, maintain a healthy lifestyle that includes frequent exercise and a well-balanced diet rich in fruits and vegetables.
Speak with your doctor about customized screening schedules and any concerns you may have about your cervical health.
Read more about breast cancer
Breast Cancer: How to Recognize Early Signs & Get Treatment
References:
Burmeister, Carly A., et al. “Cervical cancer therapies: Current challenges and future perspectives.” Tumour virus research 13 (2022): 200238.
Zhang, Shaokai, et al. “Cervical cancer: Epidemiology, risk factors and screening.” Chinese Journal of Cancer Research 32.6 (2020): 720.
Kojalo, Una, et al. “An overview of cervical cancer epidemiology and prevention in the Baltic States.” BMC Public Health 23.1 (2023): 660.
