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 gay, 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

Screening method of choiceManagement of screen resultsComments
HPV vaccinated
Age-based screening as below  
<21 years
No cervical cancer screening regardless of risk factorsNo cervical cancer screening recommendedDo not use HPV testing
21-29 years
Cervical cancer screening by cytology alone every 3 years
  • Normal cytology
    • Repeat cytology testing in 3 years
  • ASC-US cytology + HPV negative
    • Repeat cytology testing in 3 years
  • ASC-US cytology + HPV positive
  • LSIL or more severe cytology

Do not use HPV testing for screening

HPV testing is appropriate for triaging of women with abnormal cytology

30-65 years

PREFERRED

HPV and cytology cotesting every 5 years

  • Normal cytology + HPV negative
    • Repeat cotesting in 5 years
  • ASC-US cytology + HPV negative
    • Repeat cotesting in 5 years
  • Normal cytology + HPV positive
    • Option 1: Repeat cotesting in 12 months
      • If positive: follow-up with colposcopy
      • If negative: return to regular screening schedule
    • Option 2: HPV genotype 16 and 18 specific detection
      • If HPV 16 or HPV 16/18 positive: refer to colposcopy
      • If HPV 16 or HPV 16/18 negative: repeat cotesting in 12 months
  • ASC-US cytology + HPV positive
  • LSIL or more severe cytology
Screening by HPV testing alone is not recommended for most clinical settings

Acceptable

Cytology alone every 3 year

  • Normal cytology
    • Repeat cytology in 3 years
  • ASC-US cytology + HPV negative
    • Repeat cytology in 3 years
  • ASC-US cytology + HPV positive
  • LSIL or more severe cytology
 
>65 years
Prior screening was adequate and negative*No further screening*Adequate screening means 3 consecutive negative cytology results or 2 consecutive negative cotesting results within the last 10 years, most recent test within past 5 years
History of CIN2+ or more severeUse screening based on schedule for 30-65 year olds; screen for at least 20 years post positive CIN2 test 
After hysterectomy
No history of CIN2+No screening 

Diagnosis

Indications for Testing

Laboratory Testing

  • Refer to Key Points

Screening

  • Refer to Key Points

Monitoring

  • High-risk HPV DNA testing is appropriate for use in the following
    • Post-colposcopy management in women of any age with initial cytologic result of AGC or ASC-H/HSIL when initial workup does not identify a high-grade lesion
    • Post-colposcopy management in women ≥21 years with initial cytologic results of ASC-US or LSIL when initial colposcopy does not identify a high-grade lesion
    • Post-treatment surveillance
  • Refer to ASCCP guidelines  for suggested management of ASC-US, LSIL, ASC-H, HSIL, and AGC and CIN1
  • Testing for low-risk HPV genotypes has no role in evaluating women with abnormal cervical cytology

Clinical Background

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

Epidemiology

  • Prevalence – 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, SurePath Liquid-Based Pap Test 2000134
Method: Microscopy

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

For 5-year gap testing, HPV testing should be added

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

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

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

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

Reflexes to HPV DNA probe only if Pap test results are abnormal; therefore, this test cannot be used for 5-year gap testing

  
Cytology, ThinPrep® Pap with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk 8100212
Method: ThinPrep® 2000 System/Microscopy/Nucleic Acid Probe

Initial screen for cervical pathology

Only abnormal Pap test results reflex to HPV DNA probe

Results should be correlated with cytologic and histologic findings

False-negative results may occur due to inadequate cellularity

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

See 2006 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in Guidelines section of topic
Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2007893
Method: Qualitative Target Amplification Nucleic Acid Probe

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

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

Screen for cervical cancer in women ≥30 years

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

If HPV high risk is positive, HPV genotypes 16, 18/45 testing is added

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

Intended for use in

  • Women 21 years and older with ASC-US cervical cytology results
  • Women 30 years and older with positive high-risk HPV and normal cytology

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

Not intended for use as a stand-alone test

  
Human Papillomavirus (HPV) DNA Probe, High Risk (ThinPrep®) 0060750
Method: Qualitative Nucleic Acid Probe

Triage ASC-US cervical cytology in women ≥21 years

Primary screening in conjunction with cervical cytology in women ≥30 years

Follow up of treated/untreated CIN1

Determine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)

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

Results should be correlated with cytologic and histologic findings

False-negative results may occur due to inadequate cellularity

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

  
Human Papillomavirus (HPV) DNA Probe, High-Risk Surepath™  (AutoCyte) 0060744
Method: Qualitative Nucleic Acid Probe

Triage ASC-US cervical cytology in women ≥21 years

Primary screening in conjunction with cervical cytology in women ≥30 years

Follow up of treated/untreated CIN1

Determine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)

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

Results should be correlated with cytologic and histologic findings

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

False-negative results may occur due to inadequate cellularity or specimen instability due to transport in SurePath medium

  
Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene) 0065999
Method: Qualitative Nucleic Acid Probe

Primary screening in conjunction with cervical  cytology in women ≥30 years

Triage ASC-US cervical cytology in women ≥21 years to determine the need for referral to colposcopy

Determine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)

Detects high-risk HPV genotypes 16 and 18

Results should be correlated with cytologic and histologic findings

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 		 
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Human Papillomavirus (HPV) Panel by in situ Hybridization, Paraffin 2002893
Method: In situ Hybridization

Detects low-risk genotypes 6,11, and high-risk genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 66

Used to test formalin fixed, paraffin-embedded (FFPE) tissue biopsy sample

Low-risk HPV testing is not currently recommended for cervical cancer screening
Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin 2002896
Method: In situ Hybridization

Primarily of research interest

Low-risk HPV testing (genotypes 6,11) not currently part of recommended cervical cancer screening guidelines

Used to test FFPE tissue biopsy samples
Human Papillomavirus (HPV) High Risk 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