Cervical Cancer

Primary Author: Schlaberg, Robert, MD, MPH.

  • Key Points
  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

Laboratory Testing

  • HPV molecular testing, in conjunction with cytology, aids in monitoring women for recurrent disease post treatment for CIN2 or more severe grade
  • Refer to ASCCP consensus guidelines

Carcinoma of the cervix is a common cause of cancer in women worldwide, but has decreased in prominence in the U.S. with advances in screening.

Epidemiology

  • Prevalence – >12,000 new cases in the U.S. in 2014 (NCCN, 2015; ACS, 2015)
    • Third most common cancer in women worldwide
  • Age – median is 48 years
    • Infection with oncogenic strain of human papillomavirus (HPV) associated with earlier age of onset
      • High-grade dysplasia in 30s
      • Invasive carcinoma in 40s

Risk Factors

  • Sexual activity
    • Infection with oncogenic (high-risk) types of HPV
    • History of early sexual activity, especially with multiple sex partners
    • Sexual partner who began sexual activity at an early age or who had many previous sexual partners
    • History of sexually transmitted infections (STIs)
  • Family history of cervical cancer
  • Previous diagnosis of dysplasia on a Pap test or prior gynecological malignancy
  • Tobacco use
  • Exposure to diethylstilbestrol (DES) before birth
  • HIV infection
  • Weakened immune system (eg, organ transplant, chemotherapy, chronic corticosteroid use)

Pathophysiology

  • Etiology – HPV, particularly the oncogenic types
    • HPV 16 and 18 are responsible for >70% of invasive cervical cancers
  • Tumor types – 80% are squamous cell carcinoma, 20% are adenocarcinomas
    • Increased incidence of adenocarcinomas over last 30 years
      • Cytologic screening methods are less effective for adenocarcinomas, but HPV testing may improve detection rates
  • Usually evolves from cervical dysplasia
    • 30-35% of high-grade dysplasias progress to invasive carcinoma

Clinical Presentation

  • Earliest stage may be asymptomatic or have watery vaginal discharge
  • Abnormal vaginal bleeding or a significant unexplained change in menstrual cycle
  • A friable cervix that bleeds easily following intercourse or contact (eg, insertion of a diaphragm, collection of a Pap smear)
  • Pain during sexual intercourse
  • Abnormal vaginal discharge containing blood-tinged mucous

Treatment

Prevention

  • HPV vaccine – recommended for males and females 9-26 years of age in 3 doses

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Cytology, ThinPrep Pap Test and Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) (for routine co-testing in women over 30) 2000136
Method: Microscopy/Qualitative Transcription-mediated Amplification

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940
Method: Qualitative Polymerase Chain Reaction

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA) with Reflex to HPV Genotypes 16 and 18/45 by TMA, ThinPrep 2007890
Method: Qualitative Transcription-Mediated Amplification

Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
Method: Microscopy/Qualitative Transcription-mediated Amplification

Cytology, SurePath Liquid-Based Pap Test 2000134
Method: Microscopy

Cytology, ThinPrep® Pap Test 2000137
Method: ThinPrep 2000 System/Routine Cytopathologic Evaluation

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
Method: Qualitative Transcription-Mediated Amplification

Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947
Method: Qualitative Polymerase Chain Reaction

Human Papillomavirus (HPV) Genotypes 16 and 18/45 by Transcription-Mediated Amplification (TMA), ThinPrep 2007894
Method: Qualitative Transcription-Mediated Amplification

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, SurePath 2011933
Method: Qualitative Polymerase Chain Reaction

Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942
Method: Qualitative Polymerase Chain Reaction

Human Papillomavirus (HPV) 16 and 18 Genotype by PCR, SurePath 2011937
Method: Qualitative Polymerase Chain Reaction

Cytology, SurePath Liquid-Based Pap Test and Human Papillomavirus (HPV), High Risk by Hybrid Capture (for routine co-testing in women over 30) 2000133
Method: Microscopy/Qualitative Nucleic Acid Probe

Squamous Cell Carcinoma Antigen, Serum 0081054
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Limitations

Results obtained with different assay methods or kits cannot be used interchangeably

Follow Up

SCC antigen levels alone should not be interpreted as evidence of the presence or absence of malignant disease

In patients with known or expected cancer, other tests and procedures must be considered for diagnosis and patient management

Additional Tests Available

Cytology, Pap Smear 2000624
Method: Microscopy

Comments

Use for screening and detection of cervical cancer

Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin 2002899
Method: In situ Hybridization

Comments

Preferred in situ hybridization test to detect high-risk HPV subtypes (16, 18) in formalin-fixed, paraffin-embedded tissue

Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin 2002896
Method: In situ Hybridization

Comments

Preferred test is HPV high-risk in situ hybridization if determining potential cancer risk

Human Papillomavirus (HPV), High Risk by Hybrid Capture, ThinPrep 2008404
Method: Qualitative Nucleic Acid Probe

Comments

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Detects high-risk HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 associated with cervical cancer and its precursor lesions

Human Papillomavirus (HPV), High Risk by Hybrid Capture, Cervical Brush 0065999
Method: Qualitative Nucleic Acid Probe

Comments

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by Hybrid Capture 2000135
Method: Microscopy/Qualitative Nucleic Acid Probe

Comments

For HPV testing, only FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (Cytology ThinPrep Pap test with reflex to HPV by TMA)

Human Papillomavirus (HPV), High Risk by Hybrid Capture, SurePath 0060744
Method: Qualitative Nucleic Acid Probe

Comments

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (hrHPV TMA, ThinPrep; or hrHPV PCR, ThinPrep)

Guidelines

ACOG Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol. 2009; 114(6): 1409-20. PubMed

Huh W, Ault K, Chelmow D, Davey D, Goulart R, Garcia F, Kinney W, Massad S, Mayeaux E, Saslow D, Schiffman M, Wentzensen N, Lawson H, Einstein M. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol. 2015; 125(2): 330-7. PubMed

James R, Cruickshank M, Siddiqui N, Guideline Development Group. Management of cervical cancer: summary of SIGN guidelines. BMJ. 2008; 336(7634): 41-3. PubMed

Massad S, Einstein M, Huh W, Katki H, Kinney W, Schiffman M, Solomon D, Wentzensen N, Lawson H, 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013; 121(4): 829-46. PubMed

Moyer V, U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012; 156(12): 880-91, W312. PubMed

NCCN Clinical Practice Guidelines in Oncology, Cervical Cancer. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jun 2015]

Protocol for the Examination of Specimens from Patients with Carcinoma of the Uterine Cervix. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: October 2009. College of American Pathologists (CAP). Northfield, IL [Accessed: Nov 2015]

Salani R, Backes F, Fung M, Holschneider C, Parker L, Bristow R, Goff B. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011; 204(6): 466-78. PubMed

Saslow D, Solomon D, Lawson H, Killackey M, Kulasingam S, Cain J, Garcia F, Moriarty A, Waxman A, Wilbur D, Wentzensen N, Downs L, Spitzer M, Moscicki A, Franco E, Stoler M, Schiffman M, Castle P, Myers E, American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012; 137(4): 516-42. PubMed

Smith R, Manassaram-Baptiste D, Brooks D, Doroshenk M, Fedewa S, Saslow D, Brawley O, Wender R. Cancer screening in the United States, 2015: a review of current American cancer society guidelines and current issues in cancer screening. CA Cancer J Clin. 2015; 65(1): 30-54. PubMed

Trimble E. Cervical cancer state-of-the-clinical-science meeting on pretreatment evaluation and prognostic factors, September 27-28, 2007: proceedings and recommendations. Gynecol Oncol. 2009; 114(2): 145-50. PubMed

General References

References from the ARUP Institute for Clinical and Experimental Pathology®

Bentz J, Hughes J, Fatheree L, Schwartz M, Souers R, Soures R, Wilbur D, Cytopathology Resource Committee, College of American Pathologists. Summary of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program. Arch Pathol Lab Med. 2008; 132(5): 788-94. PubMed

Bentz J. Liquid-based cytology for cervical cancer screening. Expert Rev Mol Diagn. 2005; 5(6): 857-71. PubMed

Bishop J, Marshall C, Bentz J. New technologies in gynecologic cytology. J Reprod Med. 2000; 45(9): 701-19. PubMed

Hughes J, Bentz J, Fatheree L, Souers R, Wilbur D, Cytopathology Resource Committee, College of American Pathologists. Changes in participant performance in the "test-taking" environment: observations from the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program. Arch Pathol Lab Med. 2009; 133(2): 279-82. PubMed

Witt B, Factor R, Jarboe E, Layfield L. Negative loop electrosurgical cone biopsy finding following a biopsy diagnosis of high-grade squamous intraepithelial lesion: frequency and clinical significance. Arch Pathol Lab Med. 2012; 136(10): 1259-61. PubMed

Medical Reviewers

Last Update: February 2016