What are the guidelines for Human Papillomavirus (HPV) testing in clinics?

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Last updated: December 10, 2025View editorial policy

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HPV Testing in Clinics: Evidence-Based Guidelines

HPV testing in clinics should be used strategically based on patient age and clinical indication—specifically for primary screening or co-testing in women aged ≥30 years, for triage of ASC-US cytology in women aged ≥21 years, and for post-treatment surveillance, but should NOT be used as a standalone test in women under 25 years or for STD screening purposes. 1

Age-Specific HPV Testing Recommendations

Women Under 25 Years

  • Do not perform HPV testing for routine cervical cancer screening in women aged <25 years 1
  • HPV prevalence is extremely high in this age group (up to 81% in sexually active adolescents), but infections are typically transient and rarely progress to cancer 1
  • The single exception is adolescents with HIV infection, who should begin screening 1 year after onset of sexual activity but no later than age 21 years using cytology alone (not primary HPV testing) 1

Women Aged 25-29 Years

  • Pap test alone every 3 years is the recommended screening method 2, 3
  • HPV testing is not recommended for primary screening in this age group 1
  • HPV testing may be used for triage of ASC-US cytology results in women aged ≥21 years 1

Women Aged 30-65 Years

  • Co-testing (Pap test plus HPV DNA test) every 5 years is the preferred approach 2, 3
  • Acceptable alternatives include Pap test alone every 3 years or primary HPV testing alone every 5 years 2
  • Co-testing maximizes cancer prevention while reducing false-positives compared to younger age groups 2
  • Primary HPV testing shows 51% higher detection of high-grade lesions but the benefit-to-harm ratio only becomes favorable at age 30 and above 2

FDA-Cleared HPV Tests and Their Approved Uses

Tests Cleared for Primary Screening

Only two tests are FDA-cleared for primary cervical cancer screening 1:

  • Cobas 4800 HPV test (Roche Molecular Diagnostics)
  • Onclarity HPV test (Becton Dickinson)

Both detect 14 oncogenic HPV types (16,18,31,33,35,39,45,51,52,56,58,59,66,68) plus individual genotyping for types 16 and 18 1

Tests NOT Cleared for Primary Screening

The following tests should only be used with cytology or for triage of abnormal results, not as standalone primary screening 1:

  • Hybrid Capture 2 High-Risk HPV DNA test (Qiagen)
  • Cervista HPV High-Risk DNA and HPV 16/18 DNA tests (Hologics)
  • APTIMA HR HPV test (Gen Probe)

Critical pitfall: Using non-approved tests for primary screening violates FDA clearance and may lead to inappropriate patient management 1

Clinical Indications Where HPV Testing IS Appropriate

1. Triage of ASC-US Cytology

  • HPV testing is recommended for women aged ≥21 years with ASC-US results 1, 3
  • Three management options exist: HPV triage testing, repeat Pap tests at 6 and 12 months, or prompt colposcopy 2
  • This is the most cost-effective use of HPV testing in younger women 4

2. Post-Treatment Surveillance

  • HPV testing should occur at least 6-12 months after excisional or ablative therapy 1
  • A negative HPV test has 99-100% negative predictive value for remaining free of intraepithelial neoplasia 1
  • In the absence of compelling risk factors (large lesion, positive margins, endocervical involvement), test at 12 months 1

3. Follow-Up After Abnormal Screening

  • HPV testing can be used for follow-up after colposcopy with no CIN 2/3 found 1
  • Useful for monitoring after treatment of cervical precancers 1

Clinical Situations Where HPV Testing Should NOT Be Performed

The following are absolute contraindications to HPV testing 1:

  • Deciding whether to vaccinate against HPV
  • Testing for low-risk (nononcogenic) HPV types (e.g., types 6 and 11)
  • Providing care to persons with genital warts or their partners
  • Testing persons aged <25 years as part of routine cervical cancer screening
  • Testing oral or anal specimens
  • STD screening purposes 5

Common pitfall: Pap tests should not be considered screening tests for STDs, and HPV testing is not an STD screening tool 5

Special Populations

HIV-Positive Individuals

  • Do not use primary HPV testing in individuals with HIV 1
  • Use conventional or liquid-based cytology (Pap test) as the primary screening method 1
  • Co-testing (cytology and HPV test) can be done in individuals aged ≥30 years with HIV 1
  • Annual screening is recommended initially; after 3 years of consecutive normal results, the interval can be increased to every 3 years 1
  • Lifelong screening is recommended among persons with HIV infection 1

Pregnant Women

  • Follow the same screening recommendations as non-pregnant women 2, 3
  • Conventional or liquid-based cytology can be safely obtained during pregnancy 1

HPV-Vaccinated Women

  • Screen using the same recommendations as unvaccinated women 2, 3
  • Vaccination status does not change screening protocols 2, 3

Management of Discordant Results (HPV-Positive, Pap-Negative)

Approximately 5% of women have HPV-positive results with normal Pap tests 6:

  • This rate is similar across diverse populations, including underserved women 6
  • HPV 16/18 genotyping is identified in only 14% of discordant women 6
  • For women aged ≥30 years with normal cytology and positive HPV, repeat cytology at 6 and 12 months or repeat HPV testing at 12 months 1

Implementation Considerations for Clinics

Laboratory Requirements

  • All HPV testing must be performed in CLIA-certified laboratories 1
  • Use only FDA-cleared HPV assays for their approved indications 1

Patient Education Gaps

  • Only 7% of women find HPV testing acceptable as a screening method 7
  • 92.2% of women remain unaware that HPV testing can replace Pap testing for screening 7
  • Only 20.6% know that women aged 30-65 can be screened every 5 years with co-testing or primary HPV screening 7
  • Proactive patient education is essential before implementing primary HPV screening 7

Self-Collection

  • Self-collection for HPV testing is not FDA-cleared or recommended by U.S. medical organizations 1
  • While it has potential for increasing screening rates in underserved populations, it remains investigational 1

Utilization Patterns

  • Only 26.6% of eligible uninsured/underinsured women have had at least one HPV test 8
  • Among those tested, 13.3% test positive for HPV 8
  • HPV test utilization is significantly associated with age, race/ethnicity, birthplace, and area-level poverty 8

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Cervical Cancer Screening Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Cervical Cancer Screening Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

STD Screening Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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