Cervical Cancer

Clinical Background

Carcinoma of the cervix was once the most common cause of cancer in women.

Epidemiology

Prevalence - >11,000 women diagnosed in 2008
Age
- High-grade dysplasia - 30-39 years
- Invasive carcinoma - 40-49 years
15% of U.S. women 14-59 years old test positive for a high-risk strain of human papillomavirus (HPV)

Risk Factors

Sexual activity
- Infection with human papillomavirus, genital warts
- A history of sexual activity as a teenager, especially if more than 1 sex partner
- Multiple sex partners now
- A partner who began sexual activity at an early age or who had many previous sexual partners
- A history of a sexually transmitted disease
A family history of cervical cancer
A previous diagnosis of dysplasia on a Pap test or a prior gynecological malignancy
Tobacco use
Exposure to diethylstilbestrol (DES) before birth
HIV infection
Weakened immune system due to such factors as an organ transplant, chemotherapy or chronic corticosteroid use

Clinical Presentation

Abnormal vaginal bleeding or a significant unexplained change in menstrual cycle
A friable cervix that bleeds easily following intercourse or contact such as the insertion of a diaphragm or collection of a Pap smear
Pain during sexual intercourse
Abnormal vaginal discharge containing blood-tinged mucus

Pathophysiology

Etiology - human papillomavirus, an oncogenic virus, is the typical cause
- HPV 16 and 18 are responsible for >70% of invasive cervical cancers
80% are squamous cell carcinoma, 10-15% are adenocarcinoma
Usually evolves from cervical dysplasia
- 1/3 of high-grade dysplasias progress to invasive carcinoma

Treatment

Disease management guidelines are available at the following web site

Click here for consensus guidelines from American Society for Colposcopy and Cervical Pathology.

Prevention

FDA-approved quadrivalent vaccine for HPV 6, 11, 16 and 18 (Gardasil) approved for use in females 9-26 years of age

See Also

Human Papillomavirus - HPV

Sexually Transmitted Infections, Bacteria

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Cytology, SurePath™ Liquid-Based Pap Test (AutoCyte PREP™ System)

ARUP #: 8100400

Methodology: PrepStain™ Slide Processor/Routine Cytopathologic Evaluation

Use:

Intended as replacement for conventional gynecologic Pap smears for use in the screening and detection of cervical cancer, precancerous lesions, atypical cells and all other cytologic categories as defined by the Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses

Limitations:

Although this screening test has a low probability of error, patient should be reminded to consult physician immediately if she experiences any suspicious signs or symptoms, regardless of her Pap test result

Follow-up:

Women with atypical squamous cells of undetermined significance (ASC-US) should be managed using a program of either repeat cervical cytology testing, immediate colposcopy or DNA testing for high-risk types of human papillomavirus (HPV)

Test name: Cytology, SurePath™ Liquid-Based Pap Test (AutoCyte PREP™ System) with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk

ARUP #: 8100214

Methodology: PrepStain™ Slide Processor/Routine Cytopathologic Evaluation/Nucleic Acid Probe

Use:

A positive high risk HPV test result indicates that the patient may be infected with one or more of the following HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, which are associated with cervical cancer and its precursor lesions

Limitations:

Results should be correlated with cytologic/histologic findings

Cross-reactions with genotypes other than those associated with cervical cancer and its precursor lesions may occur

Follow-up:

Test name: Cytology, ThinPrep® Pap Test™

ARUP #: 8100211

Methodology: ThinPrep® 2000 System

Use:

Limitations:

Follow-up:

Test name: Cytology, ThinPrep® Pap with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk

ARUP #: 8100212

Methodology: ThinPrep® 2000 System/Routine Cytopathologic Evaluation/Nucleic Acid Probe

Use:

A positive high-risk HPV test result indicates that the patient may be infected with one or more of the following HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, which are associated with cervical cancer and its precursor lesions

Limitations:

A negative result does not rule out the presence of an HPV genotype absent for the test panel, a low level infection or specimen sampling error

Cross-reactions with genotypes other than those associated with cervical cancer and its precursor lesions may occur

Results should be correlated with cytologic/histologic findings

Follow-up:

Women with atypical squamous cells of undetermined significance (ASC-US) should be managed using a program of either repeat cervical cytology testing, immediate colposcopy, or DNA testing for high-risk types of Human Papillomavirus (HPV)

Test name: Human Papillomavirus (HPV) Panel, Paraffin

ARUP #: 8030622

Methodology: In situ Hybridization

Use:

This panel includes: Low-risk HPV (Genotypes 6, 11) and High-risk HPV (Genotypes: 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 66).

Confirm HPV cytology

Limitations:

Follow-up:

Test name: Human Papillomavirus (HPV) High Risk, Paraffin

ARUP #: 8030624

Methodology: In situ Hybridization

Use:

Includes high-risk HPV genotypes: 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 66

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene)

ARUP #: 0065999

Methodology: Nucleic Acid Probe

Use:

Detects high-risk HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk Surepath® (AutoCyte)

ARUP #: 0060744

Methodology: Nucleic Acid Probe

Use:

Detects high-risk HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk (ThinPrep®)

ARUP #: 0060750

Methodology: Nucleic Acid Probe

Use:

Detects high-risk HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68

References

Guidelines

Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith RA, Eyre HJ, Cohen C. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52(6):342-362.

Screening for cervical cancer: recommendations and rationale. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2003 Jan 22). 21 pages. NGC:002758

Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002;287(16):2120-2129.

General References

2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests. American Society for Colposcopy and Cervical Pathology (Accessed 3 May 2008)

Bishop JW, Marshall CJ, Bentz JS. New technologies in gynecologic cytology. J Reprod Med. 2000;45(9):701-719.

Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, Markowitz LE. Prevalence of HPV infection among females in the United States. JAMA. 2007;297(8):813-819.

Early Detection of Cervical Cancer. CA Cancer J Clin 2002 52: 375-376 (Accessed 3 May 2008)

Stoler MH. Human papillomavirus biology and cervical neoplasia: implications for diagnostic criteria and testing. Arch Pathol Lab Med. 2003;127(8):935-939.

Valdespino VM, Valdespino VE. Cervical cancer screening: state of the art. Curr Opin Obstet Gynecol. 2006;18(1):35-40.

ACOG Practice Bulletin: clinical management guidelines for obstetrician-gynecologists. Number 45, August 2003. Cervical cytology screening (replaces committee opinion 152, March 1995). Obstet Gynecol. 2003;102(2):417-427.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Bentz JS. Liquid-based cytology for cervical cancer screening. Expert Rev Mol Diagn. 2005;5(6):857-871.

Medical Reviewers

Bentz, Joel S., M.D., M.S. Associate Professor, Pathology, University of Utah

Carney, Heather, M.D. Assistant Medical Director, Transfusion Services at ARUP Laboratories; Pathology, University of Utah

Collins, Brian T., M.D. Medical Director, Cytopathology at ARUP Laboratories; Professor, Pathology, University of Utah

Layfield, Lester , M.D. Fine-Needle Aspiration Services and Molecular Diagnostics at ARUP Laboratories; Professor and Division Head, Anatomic Pathology, University of Utah

Comprehensive Review: January 2008
Last Update: May 2008

Screening Guidelines for Cervical Cancer
	American Cancer Society (Nov 2002)	U.S. Preventative Services Task Force (Jan 2003)	American College of Obstetricians and Gynecologists (Aug 2003)
When to initiate screening
	Approximately 3 years after onset of vaginal intercourse or age 21, whichever comes first
Recommended screening intervals
Conventional Pap	Annually; every 2-3 years for women greater than or equal to 30 with 3 negative cytology tests	At least every 3 years	Annually; every 2-3 years for women greater than or equal to 30 with 3 negative cytology tests
Liquid-based cytology	Every 2 years; every 2-3 years for women greater than or equal to 30 with 3 negative cytology tests		Annually; every 2-3 years for women greater than or equal to 30 with 3 negative cytology tests
If HPV testing used	Every 3 years if HPV negative, cytology negative		Every 3 years if HPV negative, cytology negative
When to discontinue screening
	Women greater than or equal to 70 years of age with greater than or equal to 3 recent, consecutive negative cytology tests, and no abnormal tests in the past 10 years	Women greater than or equal to 65 years of age with negative cytology tests, who are not in a high-risk category for cervical cancer
Women who are status post total hysterectomy
	May discontinue testing if hysterectomy was for benign reasons and there is no history of high-grade dysplasia (CIN)	May discontinue if hysterectomy was performed for benign indications	May discontinue testing if hysterectomy was for benign reasons and there is no history of high-grade dysplasia (CIN)