What are the methods for diagnosing Human Papillomavirus (HPV)?

Diagnosing Human Papillomavirus (HPV)

The definitive diagnosis of HPV infection depends on the detection of viral nucleic acid (DNA or RNA) or capsid protein, with different diagnostic approaches needed for visible lesions versus subclinical infection. 1

Clinical Presentation and Visual Diagnosis

• Visible genital warts: HPV infection may present as exophytic warts (condylomata acuminata) that can be diagnosed through visual inspection
• Subclinical infection: More common than visible warts and requires specific testing methods 1

Diagnostic Methods

1. Direct Visual Methods

• Visual inspection: Effective for diagnosing visible genital warts
• Acetic acid application: While sometimes used to identify "acetowhite" areas on genital skin or mucous membranes, this is not recommended as a routine screening test due to poor specificity and high false-positive rates 1
• Colposcopy: Used to examine the cervix after abnormal Pap test results, can identify HPV-related lesions

2. Molecular Testing

• HPV DNA tests: Several FDA-approved tests detect viral nucleic acid 1

  • Hybrid Capture 2 High-Risk HPV DNA test (Qiagen)
  • Cervista HPV High-Risk test (Hologics)
  • Cervista HPV 16/18 test (type-specific)
  • Digene HC2 HPV DNA test (detects 13 high-risk or 5 low-risk types)

• PCR testing: Can identify specific HPV subtypes with high sensitivity 2, 3

• RNA testing: Detection of E6/E7 oncogenic transcripts may help identify women at risk of disease progression 4

3. Cytology-Based Methods

• Pap test: Indirect method that detects cellular changes caused by HPV rather than the virus itself
  • Not specific for HPV but identifies cervical cell abnormalities that may be HPV-related
  • Pap smear diagnosis of HPV does not always correlate with detection of HPV DNA in cervical cells 1

Recommended Testing Approaches

For Women:

• Cervical screening:

  • Pap test for women 21 years and older
  • For women ≥30 years: HPV DNA testing can be used in conjunction with Pap test (adjunct testing) 1
  • Women with normal Pap tests and negative tests for high-risk HPV can extend screening interval to 3 years 1

• Abnormal Pap results:

  • High-risk HPV DNA tests are recommended for triage of women ≥21 years with ASC-US cytology results 1
  • Women with abnormal screening should be referred to providers experienced in managing these cases 1

For Men:

• No FDA-approved test for HPV in men
• Diagnosis typically made through visual identification of genital warts
• Biopsy may be performed for atypical lesions

Important Limitations and Considerations

• HPV testing is not recommended for:

  • Deciding whether to vaccinate
  • General STD screening
  • Testing adolescents <21 years
  • Primary cervical cancer screening as a stand-alone test 1

• Self-collected vaginal swabs may be an alternative to clinician-collected cervical samples for HPV testing, though cervical samples generally yield better amplification 2

• HPV infection may be active, latent, or transient, which can lead to misclassification at testing 1

• Most HPV infections, particularly in young women, are transient and resolve spontaneously without treatment 5

Clinical Pitfalls to Avoid

• Do not equate a pelvic examination with HPV testing or Pap testing - many women erroneously believe a sample was taken when only an examination was performed 1

• Avoid using acetic acid application as the sole diagnostic method for subclinical HPV infection due to high false-positive rates 1

• Remember that HPV DNA testing is not recommended for women under 21 years of age due to high prevalence of transient infections 1

• Do not make treatment decisions based solely on HPV tests for subclinical infection without coexistent dysplasia 1