Cervical Cancer Scientific Overview

- Cervical cancer is considered to be treatable and curable when identified at an early stage.

- The Human Papilloma Virus (HPV) is the main cause of cervical cancer and is sexually transmitted.

- Vaccination and cervical screening programs have significantly reduced the number of cervical cancer cases.

- Regular cervical screening is recommended for all women above the age of 25 and can help identify cervical cancer at an early and treatable stage.

Cervical cancer is the fourth most common cancer amongst women worldwide and develops in the cylinder-shaped tissue separating the uterus from the vagina, also known as the cervix. It was estimated that in 2020, 604,000 women were diagnosed with the disease and 342,000 deaths occurred worldwide whereby 90% of all new cases and deaths occurred in low and middle-income countries. This was due to the limited access to preventative measures and late-stage diagnosis of cervical cancer when the disease had greatly progressed. Cervical cancer is most often diagnosed in women aged between 35 to 45 years of age with around 20% of cases diagnosed in women aged 65 or older.  

Cervical cancer is predominantly caused by persistent Human Papilloma Virus (HPV) infection, and it is the most common HPV-related disease. HPV is sexually transmitted and approximately 80% of women will be infected with the virus throughout their lifetime, the majority of which by the time they are 45 years old. HPV infection often occurs in younger sexually active age groups, and it can take around 15 to 20 years for cervical cancer to develop in women with a normal immune system while in women with weakened immune systems (noted in patients with untreated HIV), it can take between 5 and 10 years [1, 2].  

There are over 200 different strains of HPV which have been identified and these have been categorised as either low-risk or high-risk HPV strains. Of the high-risk strains, more than 50% of all cervical cancer cases are attributed to two specific strain types: HPV-16 and HPV-18. Other risk factors for cervical cancer include sexually transmitted diseases such as HIV, chlamydia and genital herpes increasing one’s risk for HPV infection or co-infection which may weaken the immune system. Prolonged use of oral contraceptives greater than 5 years has also been associated with an increased risk of developing cervical cancer [1, 3].

Following the introduction of a number of preventative measures including vaccines and cervical screening programs, there has been a decline in the incidence of cervical cancer.

  • HPV vaccines: The first HPV vaccine was approved in 2006 and as of today there are 4 vaccines that have been prequalified by the WHO targeting nine high-risk HPV strains including HPV-16 and HPV-18. The HPV vaccine has been found to be most effective in girls between 9 to 14 years of age who have most likely not started being sexually active. It is also recommended in women up to 26 years of age. Some countries are also beginning to offer HPV vaccination to boys to help prevent HPV male related cancers [2].

  • Cervical screening: Cervical screening programs check for possible HPV infection to detect pre-cancerous, early stage, cervical cancer. Most screening programs recommend women from the age of 25 to carry out regular cervical tests every 3-5 years. Women with a weakened immune system (such as those living with HIV) are recommended to screen more frequently. To collect cervical cells, a soft brush is used to gently sweep the cervix which is then washed into a collection tube. Testing is carried out using molecular methods testing for the presence of HPV-DNA and HPV-mRNA in a cervical sample. Cervical samples can also be investigated using a classical visualisation method observing possible cervical variations as well as visualisation of the cells (cytology) looking for possible cancerous changes. The WHO revised their cervical screening guidelines in 2021 recommending molecular testing as the preferred method over the classic Pap smear method as it is more cost-effective and sensitive method compared to the classic visual inspection techniques [3].  

Early-stage cervical cancer often displays no symptoms (asymptomatic), and patients may present with irregular or heavy vaginal bleeding, unusual vaginal discharge or may be diagnosed as a result of a cervical screening test. Patients with advanced disease can present with pelvic or lower-back pain as well as bladder or bowel changes leading to blood in the urine or stool. Pelvic examination, blood tests (especially kidney function) and colposcopy (biopsy of the cervix itself) allow for further investigation if cervical cancer is suspected.

Cervical cancer is divided into 5 different stages depending on the severity of the condition:

  • Stage 0: This stage is also known as carcinoma in situ (CIN) or pre-cancerous phase and defines the presence of abnormal cells in the inner lining of the cervix .
  • Stage I: This stage is defined by the presence of cancerous cells in the cervix only. It is subdivided into two additional stages, IA and IB, based on the size of the tumour.
  • Stage II: Cancer spread is noted beyond the cervix and to the upper two-thirds of the vagina, but there is no spread to the pelvic wall. It is also subdivided into substages (IIA1, IIA2 and IIB) based on the size of the tumour and spread beyond the cervix to the uterus.
  • Stage III: In this stage, cervical cancer has spread to the lower third of the vagina and/or to the pelvic wall. This stage also includes kidney problems and the involvement of lymph nodes. Stage III is subdivided into Stage IIIA, IIIB and IIIC based on how far the cancer has spread from the cervix.
  • Stage IV: In this stage of the disease, cervical cancer has spread (metastasised) beyond the pelvis to other parts of the body including the bladder, rectum, lungs, liver, and bones. It is subdivided into stages IVA and IVB according to where the cancer has spread [1-3].

Cervical cancer is considered to be treatable and curable if diagnosed at an early stage with a 5-year relative survival rate of 92%. In order to choose the appropriate treatment for cervical cancer, the staging itself as well as location and size of the tumour are of utmost importance. Fertility preservation is a crucial factor to consider when deciding on a treatment plan [4].  

Early-stage cervical cancer is considered for disease localised to the cervix and uterus (Stages IA to Stage IB – including all subtypes). Diagnosis is made following a cervical biopsy and histological examination. The primary treatment offered to patients with early-stage cervical cancer include fertility preserving surgery (i.e., conization, trachelectomy), hysterectomy (i.e., extrafascial, modified radical, radical) or radiation with or without chemotherapy. Surgery is often preferred as the primary therapy over radiation in patients with early-phase cervical cancer to preserve ovarian function and avoid possible decrease in quality-of-life following radiation therapy. If a patient is highly likely to develop disease recurrence, adjuvant therapy (chemotherapy administered after surgery) is recommended. Cervical cancer patients who have undergone treatment should be followed up accordingly in order to detect any possible recurrence at an early stage [5-7].  

Locally advanced cervical cancer is defined as one which has spread beyond to and beyond the reproductive track to include the pelvic wall, mucosa of the bladder or rectum, or involves pelvic lymph nodes (Stage3 III-IVA). The primary treatment in these advanced cases is chemoradiation therapy (combination of chemotherapy and radiation). Chemotherapy is administered as single or combination agents. Radiation therapy is often administered directly to the pelvis in an effort to maximise local control and brachytherapy focuses radiation to the cervix/vaginal area to focus the radiation. In patients with a higher risk of relapse, removal of the uterus (hysterectomy) may be recommended following chemoradiation. Post-treatment surveillance is carried out to observe for possible recurrences [6-8].

An initial diagnosis of metastatic cervical cancer (Stage IVB) is uncommon but can develop within the first two years of treatment completion for 15-61% of women. It is incurable in the majority of cases. Recurrent cervical cancer patients present with local recurrence or metastatic spread to other part of the body. In the case of local recurrence, women may present with disease relapse localised to the cervix or vagina. Treatment is dependent on the patient’s prior therapy. Localised surgery (such as pelvic exenteration) or hysterectomy may be offered to patients who have received radiation therapy previously. Radiation therapy or chemotherapy may be offered to patients if not received previously. In the case of metastatic disease, management is dependent on the presentation of the disease itself. In some cases, the metastatic disease may be resectable through surgery. However, there is a poorer prognosis for patients presenting with disease isolated to the lymph nodes or other locations in the body such as the lung, liver and bones with some experts recommending systemic chemotherapy while others recommend radiation therapy with or without chemotherapy [6, 7, 9].  

1. (WHO), W.H.O. Cervical Cancer. 2022; Available from: https://www.who.int/news-room/fact-sheets/detail/cervical-cancer.

2. Cohen, P.A., et al., Cervical cancer. Lancet, 2019. 393(10167): p. 169-182.

3. Johnson, C.A., et al., Cervical Cancer: An Overview of Pathophysiology and Management. Semin Oncol Nurs, 2019. 35(2): p. 166-174.

4. Cervical Cancer Prognosis and Survival Rates. 2022  [cited 2023.

5. J Michael Straughn, J., MDCatheryn Yashar, MD. Management of early-stage cervical cancer. 2022; Available from: https://www.uptodate.com/contents/management-of-early-stage-cervical-cancer?search=cervical%20cancer&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2.

6. HelseDirektoratet. 4. Behandling av livmorhalskreft. 2022; Available from: https://www.helsedirektoratet.no/nasjonale-forlop/livmorhalskreft/behandling-av-livmorhalskreft#hovedgrupper-av-behandlingsforlop.

7. Network, N.C.C. Cervical Cancer. 2022; Available from: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf.

8. J Michael Straughn, J., MDCatheryn Yashar, MD. Management of locally advanced cervical cancer. 2022; Available from: https://www.uptodate.com/contents/management-of-locally-advanced-cervical-cancer?search=cervical%20cancer&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3.

9. Jason D Wright, M. Management of recurrent or metastatic cervical cancer. 2022; Available from: https://www.uptodate.com/contents/management-of-recurrent-or-metastatic-cervical-cancer?search=cervical%20cancer&source=search_result&selectedTitle=10~150&usage_type=default&display_rank=9.

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