Cervical Cancer

Key Points

HPV Testing in Women

Diagnosis

Indications for Testing

Laboratory Testing

  • Refer to Key Points in HPV topic

Screening

Monitoring

  • 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

Clinical Background

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

Epidemiology

  • Prevalence – estimated 12,200 new cases in the U.S. in 2010
    • 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 
      • 15% of U.S. women 14-59 years test positive for a high-risk strain 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 a 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

  • FDA-approved recombinant vaccine (Gardasil) is effective against HPV types 6, 11, 16 and 18 and is approved for use in males and females 9-26 years

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
Test Name and Number Recommended Use Limitations Follow Up
Cytology, ThinPrep® Pap Test 2000137
Method: ThinPrep® 2000 System/Routine Cytopathologic Evaluation

An acceptable test for all women for 3-year interval cervical cancer screening

An acceptable test for cervical cancer screening cotesting option (5-year interval testing) in women 30-65 years when ordered in conjunction with HPV testing (eg, Human Papillomavirus [HPV], High Risk, E6/E7 mRNA by Transcription-Mediated Amplification)

 

Refer to Key Points in HPV topic

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

May be used for routine 3-year interval cervical cancer screening test in all women

For 5-year interval testing (cotesting) in women 30-65 years, order with HPV test (eg, Human Papillomavirus [HPV], High Risk, E6/E7 mRNA by Transcription-Mediated Amplification)

This is a screening test (moderate sensitivity), not a diagnostic test (low specificity)

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when stability requirements are exceeded)

Refer to Key Points in HPV topic

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

A preferred test for cervical cancer screening cotesting option (5-year interval testing) in women ≥30 years

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

 

Refer to Key Points in HPV topic

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

Cotest for cervical cancer screening option (5-year interval testing) for women ≥30

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Available for University of Utah clients only

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when stability requirements are exceeded)

Refer to Key Points in HPV topic

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

For 3-year interval cervical cancer screening

  • A preferred test for women 21-29 years
  • An acceptable test for women 30-65 years

5-year screening interval cotesting (cytology and HPV) is preferred in women ≥30

  • Refer to 1 of the 2 cotests - Cytology, SurePath and HPV High Risk, or Cytology Thin Prep and HPV High Risk

Because this is a reflex test, triage HPV testing is performed only for abnormal cytology (ASC-US)

  • This test does not meet the requirements for cotesting (5-year interval testing, which requires both cytology and HPV testing)

False-negative results may occur due to inadequate cellularity

Cross-reactions with other genotypes (eg, low-risk) may occur

Refer to Key Points in HPV topic

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

A routine cervical cancer screening test for women 21-65 years; requires 3-year screening interval

Because this is a reflex test, triage HPV testing is performed only for abnormal cytology (ASC-US)

  • This test does not meet the requirements for cotesting (5-year interval testing, which requires both cytology and HPV testing)

For 5-year screening interval, cotesting (cytology and HPV) is preferred (eg, Cytology Thin Prep and HPV High Risk)

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when stability requirements are exceeded)

Refer to Key Points in HPV topic

Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) with Reflex to Genotypes 16 and 18/45 2007890
Method: Transcription-mediated Amplification

Use in conjunction with cytology (Pap smear) for primary cervical cancer screening in women ≥30 years

Knowledge of genotype is useful in triaging women to colposcopy who are cytology-negative (NILM) and HPV-positive

 

Refer to Key Points in HPV topic

Human Papillomavirus (HPV) Genotypes 16 and 18/45, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2007894
Method: Transcription-mediated Amplification

Acceptable test for triaging women >30 years with negative cervical cytology (NILM Pap smear) and known positive HPV

Detects E6/E7 viral messenger RNA in only the high-risk HPV types 16, 18, and 45

Does not differentiate between type 18 and 45

Sensitivity may be affected by specimen collection methods, stage of infection, and the presence of interfering substances

Refer to Key Points in HPV topic

Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2007893
Method: Transcription-mediated Amplification

A preferred test for cervical cancer screening cotesting option (5-year interval testing) in women ≥30 years when ordered in conjunction with cytology

Triage women with equivocal or mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Detects E6/E7 viral messenger RNA of the high-risk HPV genotypes associated with cervical cancer and its precursor lesions (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

Does not differentiate between types

Cross-reactivity with low-risk HPV genotypes 26, 67, 70, and 82 may occur

Sensitivity may be affected by specimen collection methods, stage of infection, and the presence of interfering substances

Refer to Key Points in HPV topic

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

A preferred test for cervical cancer screening cotesting option (5-year interval testing) in women ≥30 years when ordered in conjunction with cytology

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

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

False-negative results may occur due to inadequate cellularity

Cross-reactions with other genotypes may occur

Refer to Key Points in HPV topic

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

May be helpful in monitoring for recurrent disease

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

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

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

When ordered in conjunction with cytology, a cotesting option ( 5-year interval testing) in women ≥30 years

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

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

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when  stability requirements are exceeded)

Cross-reactions with other genotypes may occur

Refer to Key Points in HPV topic

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

An acceptable test for 3-year interval cervical cancer screening

Cannot use for cancer screening cotesting option (5-year interval testing) unless 2 specimens are submitted simultaneously (one is sent to cytology lab; the other is sent to HPV testing lab)

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

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

False-negative results may occur due to inadequate cellularity

Detects high-risk HPV genotypes 16 and 18 only; cross reactivity with high levels of high-risk HPV genotype 31 has been observed and may return an HPV 16-positive result

Refer to Key Points in HPV topic

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Cytology, Pap Smear 2000624
Method: Microscopy

Use for screening and detection of cervical cancer

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

Detects high-risk genotypes16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 66 (associated with cervical cancer and precursor lesions)

Used to test FFPE tissue biopsy samples