Cervical cancer overview

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Differentiating Cervical Cancer from other Diseases

Epidemiology and Demographics

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Cervical Cancer During Pregnancy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

Overview

Cervical cancer once was one of the leading cause of cancer-related death in the US and worldwide before the introduction of Pap smear and screening, now ranked 14th in terms of frequency in US. Cervical cancer is malignant cancer of cervix. It may present with vaginal bleeding but symptoms may be absent until cancer is in its advanced stages. Treatment consists of surgery in the early stages and chemotherapy and radiotherapy in advanced stages of the disease. An effective HPV vaccine against the two most common cancer-causing strains of HPV has recently been licensed in the US. These two HPV strains together are responsible for approximately 70% of all cervical cancers. The high risk HPV E6 and E7 gene products which are involved in viral replication and oncogenesis bind to p53 and prevents its normal activities which is G1 arrest, apoptosis, and DNA repair.The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years and for women aged 30 to 65 years, every 3 years with cervical cytology alone, every 5 years with high-risk human papillomavirus (hrHPV) testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting). The most important risk factors associated with the infection by HPV are sexual intercourse at early age at the start of the first sexual relationships, having high number of sexual partners throughout life, or women being with men having multiple sexual partners. Male circumcision and use of condoms are factors that can reduce, but not preventing the transmission of human papilloma virus.Treatment of cervical neoplasia depends upon stage of cancer at the time of presentation, it is consisit of surgical procedure like hysterectomy, or/and radiation and chemotherapy.

Historical Perspective

  • In 400 BC, Hippocrates referred to cervical cancer as cancer of the uterus, it was little known about cervical cancer until the Rennaissance era.
  • In 1842, an Italian physician named Rigoni-stern noticed that cancer of the cervix prevalence was high among married and widowed women and low or rare among the unmarried women and absent in Italian nuns.

Classification

  • Cervical cancer may be classified into many subtypes based on FIGO classification. In stage I, carcinoma is strictly confined to the cervix, in stage II, the carcinoma invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall.

Pathophysiology

HPV plays main role in pathogenesis of cervical cancer and it is widely related to disrupting cell cycle growth and regulations, summary of these include:

  • The high risk HPV E6 and E7 gene products which are involved in viral replication and oncogenesis bind to p53 and prevents its normal activities which is G1 arrest, apoptosis, and DNA repair.

Differential diagnosis

Epidemiology and Demographics

  • In terms of frequency, cervical cancer is ranked 14th now in the US but still is very common in the least developed countries.
  • In United State, cervical cancer is more common among Hispanics, African-Americans, Asians and Pacific islanders, and followed by whites. Native Alaskans and Indians have the lowest rate. Age of diagnosis is usually above 30 years old, women in their midlife.
  • Number of new cases of cervical cancer was 7.4 per 100,000 women per year and the number of deaths was 2.3 per 100,000 women per year based on statistical data collected in 2015.

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

  • Physical examination of patients with late cervical cancer is usually remarkable for cervical mass, pallor, and pedal edema.Most women with cervical cancer are asymptomatic at early stage of disease, those patients in advance stage of cancer may have symptoms like abnormal vaginal bleeding, vaginal dyscharge, abdominal and pelvic pain, urinary hesitancy.[1][2]

Chest Xray

  • Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis. It has limited value in initial work up for cervical cancer, unless there is a metastasis to the lungs and that usually happens in advances stage of cancer.

CT

Computerised tomography (CT) is used for clinical staging of cervical carcinoma, it improves the accuracy of staging based on FIGO guidelines. CT scan is useful in evaluating the followings:[3]

MRI

  • Pelvic MRI is helpful in the diagnosis of cervical cancer. In patients with advanced disease, there are several findings on MRI studies which may help early prediction of the therapeutic outcome, tumor size reduction, myometrial invasion, lymph node invasion more accurately.[4]

Ultrasound

  • Transvaginal color doppler ultrasound can be used in predicting response to chemotherapy in women with cervical cancer.

Other Diagnostic Studies

  • Cervical biopsy is the confirmatory test for the diagnosis of cervical cancer or pre-cancer.
  • Biopsy: Most women have tissue removed in the doctor's office with local anesthesia. A pathologist checks the tissue under a microscope for abnormal cells.
    • Punch biopsy: The doctor uses a sharp tool to pinch off small samples of cervical tissue.
    • Loop electrosurgical excision procedure(LEEP): The doctor uses an electric wire loop to slice off a thin, round piece of cervical tissue, this method allows deep excision of the transformation zone.
    • Endocervical curettage: The doctor uses a curette (a small, spoon-shaped instrument) to scrape a small sample of tissue from the cervix. Some doctors may use a thin, soft brush instead of a curette.
    • Conization: A conization, or cold knife cone biopsy, cone shaped samples are removed from cervix and allows for accurate examination of biopsy speciemen by pathologists.This can be done in doctor's office or in the hospital under general anesthesia. Most significant complication of this method is hemorrhage. There is relative contraindication for pregnant women and also conization increase the risk of preterm birth. [5][6]

Treatment

Medical therapy

Surgery

Cervical cancer during pregnancy

  • During pregnancy, no therapy is warranted for preinvasive lesions of the cervix, including carcinoma in situ, although expert colposcopy is recommended to exclude invasive cancer. Patients with early stage (IA) disease may safely undergo fertility-sparing treatments.
  • For patients with advanced disease, waiting for viability is generally not acceptable.
  • The standard of care is curative intent chemotherapy and radiation therapy.

Primary Prevention

  • Prevention of cervical cancer includes a comprehensive approach involving awareness, screening, and preventative vaccinations.

References

  1. Kim, Soo Hyun; Kang, Sokbom; Kim, Yong-Man; Kim, Byoung-Gie; Seong, Seok Ju; Cha, Soon Do; Park, Chan-Yong; Yun, Young Ho (2010). "Prevalence and Predictors of Anxiety and Depression Among Cervical Cancer Survivors in Korea". International Journal of Gynecological Cancer. 20 (6): 1017–1024. doi:10.1111/IGC.0b013e3181e4a704. ISSN 1048-891X.
  2. Mwaka, Amos Deogratius; Okello, Elialilia Sarikiaeli; Wabinga, Henry; Walter, Fiona M (2015). "Symptomatic presentation with cervical cancer in Uganda: a qualitative study assessing the pathways to diagnosis in a low-income country". BMC Women's Health. 15 (1). doi:10.1186/s12905-015-0167-4. ISSN 1472-6874.
  3. Prasad TV, Thulkar S, Hari S, Sharma DN, Kumar S (May 2014). "Role of computed tomography (CT) scan in staging of cervical carcinoma". Indian J. Med. Res. 139 (5): 714–9. PMC 4140036. PMID 25027081.
  4. Li, Haoran; Wu, Xiaohua; Cheng, Xi (2016). "Advances in diagnosis and treatment of metastatic cervical cancer". Journal of Gynecologic Oncology. 27 (4). doi:10.3802/jgo.2016.27.e43. ISSN 2005-0380.
  5. . doi:10.1097/IGC.0000000000000991. Check |doi= value (help). Missing or empty |title= (help)
  6. Castanon A, Brocklehurst P, Evans H, Peebles D, Singh N, Walker P, Patnick J, Sasieni P (August 2012). "Risk of preterm birth after treatment for cervical intraepithelial neoplasia among women attending colposcopy in England: retrospective-prospective cohort study". BMJ. 345: e5174. doi:10.1136/bmj.e5174. PMC 3421237. PMID 22899563.

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