eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Oncology

Cervical Cancer

Author: Agustin A Garcia, MD, Associate Professor of Medicine, University of Southern California Keck School of Medicine
Contributor Information and Disclosures

Updated: Aug 26, 2009

Introduction

Background

Cervical cancer is the second most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries. In the United States, cervical cancer is relatively uncommon. The incidence of invasive cervical cancer has declined steadily in the United States over the past few decades; however, it continues to rise in many developing countries. The change in the epidemiological trend in the United States has been attributed to mass screening with Papanicolaou tests.

Cervical carcinoma with adnexa.

Cervical carcinoma with adnexa.

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Cervical carcinoma with adnexa.

Cervical carcinoma with adnexa.



For related information, please see Medscape's Cervical Cancer Resource Center.

Frequency

United States

The American Cancer Society has estimated that in the United States in 2009, 11,270 new cases of cervical cancer will be diagnosed.1 In addition, more than 50,000 cases of carcinoma in situ are diagnosed each year.

International

Internationally, 500,000 new cases are diagnosed each year.

Mortality/Morbidity

The American Cancer Society estimates that 4,070 women will die from cervical cancer in the United States in 2009.1 This represents 1.3% of all cancer deaths and 6.5% of deaths from gynecologic cancers.

Race

In the United States, cervical cancer is more common in Hispanic, African American, and Native American women than in white women.

Sex

Cervical cancer is found only in women.

Age

Cervical cancers usually affect women of middle age or older, but it may be diagnosed in any reproductive-aged woman.

Clinical

History

  • Because women are screened routinely, the most common finding is an abnormal Papanicolaou test result.
  • Clinically, the first symptom is abnormal vaginal bleeding, usually postcoital.
  • Vaginal discomfort, malodorous discharge, and dysuria are not uncommon.
  • The tumor grows by extending upward to the endometrial cavity, downward to the vagina, and laterally to the pelvic wall. It can invade the bladder and rectum directly.
    • Symptoms that can evolve, such as constipation, hematuria, fistula, and ureteral obstruction with or without hydroureter or hydronephrosis, reflect local organ involvement.
    • The triad of leg edema, pain, and hydronephrosis suggests pelvic wall involvement.
  • The common sites for distant metastasis include extrapelvic lymph nodes, liver, lung, and bone.

Physical

  • In patients with early-stage cervical cancer, physical examination findings can be relatively normal.
  • As the disease progresses, the cervix may become abnormal in appearance, with gross erosion, ulcer, or mass. These abnormalities can extend to the vagina.
  • Rectal examination may reveal an external mass or gross blood from tumor erosion.
  • Bimanual examination findings often reveal pelvic metastasis.
  • Leg edema suggests lymphatic/vascular obstruction from tumor.
  • If the disease involves the liver, hepatomegaly may develop.
  • Pulmonary metastasis usually is difficult to detect upon physical examination unless pleural effusion or bronchial obstruction becomes apparent.

Causes

Early epidemiological data demonstrated a direct causal relationship between cervical cancer and sexual activity. Major risk factors observed include sex at a young age, multiple sexual partners, promiscuous male partners, and history of sexually transmitted diseases. However, the search for a potential sexually transmitted carcinogen was unsuccessful until breakthroughs in molecular biology enabled scientists to detect viral genome in cervical cells.

Strong evidence now implicates human papillomaviruses (HPVs) as prime suspects. HPV viral DNA has been detected in more than 90% of squamous intraepithelial lesions (SILs) and invasive cervical cancers compared with a consistently lower percentage in controls. Both animal data and molecular biologic evidence confirm the malignant transformation potential of papilloma virus–induced lesions. SILs are found predominantly in younger women, while invasive cancers are detected more often in women 10-15 years older, suggesting slow progression of cancer.

HPV infection occurs in a high percentage of sexually active women. Most of these infections clear spontaneously within months to a few years, and only a small proportion progress to cancer. This means that other crucial factors must be involved in the process of carcinogenesis.

Three main factors have been postulated to influence the progression of low-grade SILs to high-grade SILs. These include the type and duration of viral infection, with high-risk HPV type and persistent infection predicting a higher risk for progression; host conditions that compromise immunity, such as multiparity or poor nutritional status; and environmental factors such as smoking, oral contraceptive use, or vitamin deficiencies. In addition, various gynecologic factors, including age of menarche, age of first intercourse, and number of sexual partners, significantly increase the risk for cervical cancer.

  • Human papillomavirus
    • HPV is a heterogeneous group of viruses that contain closed circular double-stranded DNA. The viral genome encodes 6 early open reading frame proteins (ie, E1, E2, E3, E4, E6, E7), which function as regulatory proteins, and 2 late open reading frame proteins (ie, L1, L2), which make up the viral capsid.
    • To date, 77 different genotypes of HPV have been identified and cloned, among which, types 6, 11, 16, 18, 26, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 66, and 68 have the propensity to infect anogenital tissues.
    • The HPVs that infect the human cervix fall into 2 broad categories. The low-risk types, HPV 6b and 11, are associated with low-grade SILs but are never found in invasive cancer. The high-risk types, mostly HPV 16 and 18, are found in 50-80% of SILs and in up to 90% of invasive cancers. Although less common, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should also be considered carcinogenic.
    • The major difference between the 2 types is that after infection, the low-risk HPVs are maintained as extrachromosomal DNA episomes, while the high-risk HPV genome is found integrated into the host cellular DNA. The recombination event often leaves E6 and E7 directly coupled to the viral promoter and enhancer sequences, allowing their continued expression after integration. Because E7 binds and inactivates the Rb protein while E6 binds p53 and directs its degradation, the functional loss of both TP53 and the RB genes leads to resistance to apoptosis, causing uncensored cell growth after DNA damage. This ultimately results in progression to malignancy.
  • Human immunodeficiency virus
    • The role of human immunodeficiency virus (HIV) infection in the pathogenesis of cervical cancer is not fully understood. Studies have shown a higher prevalence of HPV in HIV-seropositive women than in seronegative women, and the HPV prevalence was directly proportional to the severity of immunosuppression as measured by CD4 counts.
    • Impaired lymphocyte function has been postulated to enhance latent or subclinical HPV activity, resulting in a higher rate of persistent infection.
    • Whether HIV has a synergistic effect on HPV infection, either by direct molecular interaction or through an indirect immunologic effect, remains unclear.

More on Cervical Cancer

Overview: Cervical Cancer
Differential Diagnoses & Workup: Cervical Cancer
Treatment & Medication: Cervical Cancer
Follow-up: Cervical Cancer
Multimedia: Cervical Cancer
References
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Further Reading

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Keywords

cervical cancer, cervix cancer, cervical cancer symptoms, cervical cancer treatment, human papillomavirus, HPV cervical cancer, cervical neoplasms, uterine cervical cancer, sexually transmitted disease, STD, vaginal cancer, vagina cancer, Papanicolaou tests, Pap smear, gynecological cancer, gynecologic cancer

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Contributor Information and Disclosures

Author

Agustin A Garcia, MD, Associate Professor of Medicine, University of Southern California Keck School of Medicine
Agustin A Garcia, MD is a member of the following medical societies: American Society of Clinical Oncology and European Society for Medical Oncology
Disclosure: Nothing to disclose.

Medical Editor

John J Kavanagh Jr, MD, Chief, Professor, Department of Internal Medicine, Section of Gynecological and Medical Therapeutics, MD Anderson Cancer Center, University of Texas College of Medicine
John J Kavanagh Jr, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association for the History of Medicine, American College of Physicians, American Federation for Medical Research, American Medical Association, Society of Gynecologist Oncologists, Southern Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital, Mammoth Lakes, California, Pioneer Valley Hospital, Salt Lake City, Utah, Warren General Hospital, Warren, Pennsylvania and Mountain West Hospital, Tooele, Utah
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD, Professor, Coordinator of Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.

 
 
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