Serum Testing for HPV Infections
Serum testing for HPV antibodies is not recommended for routine screening of HPV infections, diagnosis of cervical cancer, or management of abnormal cervical cytology results. 1, 2
Why Serum HPV Testing Is Not Used
HPV DNA testing is only FDA-approved for use with cervical specimens collected during clinical examinations, not for serum or blood samples. 2, 3 The available FDA-cleared tests (such as Hybrid Capture 2, Cervista HPV, and Cobas 4800) detect viral nucleic acid (DNA or mRNA) from cervical samples and are specifically designed for cervical cancer screening applications. 1, 2
What HPV Testing Actually Means in Clinical Practice
When guidelines refer to "HPV testing," they are exclusively discussing cervical HPV DNA/RNA testing, not serologic antibody testing. 4, 2 The recommended applications are:
Primary Screening Uses
- Women aged 30-65 years: Primary HPV testing every 5 years (preferred method), or cotesting (HPV + cytology) every 5 years, or cytology alone every 3 years 4, 5
- Women aged 25-29 years: Cytology alone every 3 years; HPV testing is NOT recommended for primary screening in this age group 4, 3
- Women under age 21: No screening of any kind, regardless of sexual history 4, 3
Triage Applications
- ASC-US cytology results: HPV testing (from cervical specimens) is recommended for triage in women aged ≥21 years 1, 4
- This "reflex HPV testing" helps determine which women with equivocal cytology need colposcopy 2
Post-Treatment Surveillance
- HPV testing has excellent negative predictive value (99-100%) for detecting persistent or recurrent disease after treatment of cervical precancers 1
- Testing should occur at least 6-12 months after treatment to allow time for viral clearance 1, 2
Situations Where HPV Testing Should NOT Be Used
The CDC explicitly states that HPV DNA testing (and by extension, any form of HPV testing including serum) is not recommended for: 1, 2
- Screening men for HPV infection
- Testing sexual partners of women with HPV
- Screening adolescents aged <21 years
- Deciding whether to vaccinate for HPV
- General STD screening purposes
- Diagnosing genital warts or other HPV-related conditions besides cervical disease
Critical Counseling Points
When discussing HPV with patients, providers should emphasize: 2
- HPV infections are extremely common and often shared between partners
- It is usually impossible to determine when or from whom infection was acquired
- HPV can remain dormant and reactivate years after initial exposure
- A positive HPV test does not indicate cancer or sexual infidelity
- Partners do not need HPV testing 2
Common Pitfalls to Avoid
- Never order serum HPV antibody testing for screening, diagnosis, or management of cervical disease—it has no validated clinical role 1, 2
- Never use HPV testing in women under 30 for primary screening, as the high prevalence of transient infections causes excessive false-positives 4, 3
- Never screen women under 21, as this leads to unnecessary procedures for lesions with high natural regression rates 4, 3
- Never assume HPV testing can replace screening in vaccinated women—they require the same screening as unvaccinated women 4, 3