Cervical cancer overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Cervical cancer once was one of leading cause of cancer related death in US and worldwide before 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 the cancer is in its advanced stages. Treatment consists of surgery (including local excision) in 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 U.S. (see Vaccine section, below). These two HPV strains together are responsible for approximately 70% of all cervical cancers. 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.
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.
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.
- HPV enters the host cell which are squamous cells of epithelium in cervix, mainly in junctional zone, between the columnar epithelium of the endocervix and the squamous epithelium of the ectocervix and that is how viral transcription and replication begins.
- HPV infection of the basal layer of epithelium takes place by attachement via different mechanism of entry, this happens by cell surface heparan sulfate, stabilizing protoglycans and Integrin.
Differential diagnosis
Cervical cancer must be differentiated from other diseases that cause abnormal vaginal bleeding, such as cervical polyp, cervical leiomyoma, invasion of the cervix from primary uterine malignancy, vaginal cancer, cervical lymphoma, adenoma malignum, metastases to cervix, and cervical ectopic pregnancy.
Epidemiology and Demographics
In terms of frequency, cervical cancer is ranked 14th now in the US but still is very common in least developed countries. In United State, cervical cancer is more common among Hispanics, African-Americans, Asians and pascific 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 number of deaths was 2.3 per 100,000 women per year based on statistical datas collected on 2015.
Risk Factors
The most potent risk factor in the development of cervical cancer is Human papillomavirus (HPV) infection. Other risk factors include smoking, increased number of sexual partners, and young age at time of first sexual intercourse, high parity, use of oral contraceptives, immunodefieciency.
Screening
According to the American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology, screening for cervical cancer by pap smear is recommended every 3 years among women age 21.
Natural History, Complications and Prognosis
If left untreated, 30-70% of patients with in situ cervical cancer may progress to develop cervical cancer. Common complications of cervical cancer include vaginal bleeding, fistula and renal failure. Prognosis is generally good, and the 5 year survival rate of patients with cervical cancer is approximately 67.9%.
Diagnosis
Staging
Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervicalcurettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervicalconization.
History and Symptoms
Physical examination of patients with late cervical cancer is usually remarkable fore cervical mass, pallor, and pedal edema.
Chest Xray
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis. It has limited value in intial work up for cervical cancer, unless there is a metastasis to the lungs and that usually happens in advances stage of cancer.
CT
CT scan may be helpful in the diagnosis of cervical cancer.
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.
Ultraasound
On ultraasound, cervical cancer is characterized by hypoechoic, heterogeneous mass involving the cervix.
Other Diagnostic Studies
Cervical biopsy is the confirmatory test for the diagnosis of cervical cancer or pre-cancer.
Treatment
Medical therapy
The optimal therapy for cervical cancer depends on the stage at diagnosis.
Surgery
The feasibility of surgery depends on the stage of cervical cancer at diagnosis.
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.