Human Papillomavirus - HPV

Key Points

HPV Testing in Men

  • Summary of recommendations
    • Screening for anal cancer is not routinely recommended for men
      • HPV testing is not currently recommended for anal cancer screening
      • No HPV test is approved by the FDA for testing of men
      • Some experts recommend yearly anal cancer screening by cytology ("anal pap") for homosexual, bisexual, and HIV-positive men (anal cancer is more common in these populations)
    • HPV is associated with the development of penile cancer
      • Screening tests are not available for penile cancer
    Source: http://www.cdc.gov/std/HPV/stdfact-hpv-and-men.htm

HPV Testing in Women

Diagnosis

Indications for Testing

Laboratory Testing

  • Refer to Key Points tab

Screening

  • Refer to Key Points tab

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

Human papillomavirus (HPV) is the most common sexually transmitted viral infection.

Epidemiology

  • Incidence – 20 million currently infected in the U.S.
  • Transmission – sexual contact (vaginal, oral, anal)

Organism

  • DNA virus
  • Multiple genotypes (>100) of varying infectivity
    • >30 types are sexually transmitted
  • Etiologic agent for most cases of cervical cancer

Pathophysiology

  • Persistent infection with oncogenic (high-risk) HPV genotypes associated with increased risk for developing high-grade dysplasia and cervical, vulvar, or vaginal carcinoma
  • Most women infected with high-risk genital HPV do not develop cancer; they clear the infection, usually within 2 years

Clinical Presentation

  • Frequently asymptomatic
  • Abnormal Pap smear
  • Complications – cervical, vaginal, vulvar carcinoma

Prevention

  • HPV vaccine – recommended for males and females 9-26 years 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
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 co-testing 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 tab

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 (co-testing) 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 tab

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 co-testing 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 tab

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

Co-test 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 tab

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 co-testing (cytology and HPV) is preferred in women ≥30

  • Refer to 1 of the 2 co-tests – 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 co-testing (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 tab

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 co-testing (5-year interval testing, which requires both cytology and HPV testing)

For 5-year screening interval, co-testing (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 tab

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

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 tab

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

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

Refer to Key Points tab

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

A preferred test for cervical cancer screening co-testing 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 tab

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

A preferred test for cervical cancer screening co-testing 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 tab

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

When ordered in conjunction with cytology, this test is a co-testing 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 tab

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 co-testing 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

Cross-reactions with other genotypes may occur

Refer to Key Points tab

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin 2002899
Method: In situ Hybridization

In situ hybridization test to detect high-risk HPV subtypes in formalin-fixed, paraffin-embedded tissue

Detects high-risk genotypes associated with cervical cancer and precursor lesions (16, 18)

Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin 2002896
Method: In situ Hybridization
Not recommended for clinical use