Do we test for Human Papillomavirus (HPV) mRNA in 25-year-olds?

HPV mRNA Testing Should Not Be Performed in 25-Year-Olds for Cervical Cancer Screening

HPV testing, including mRNA testing, should not be performed in persons aged <25 years as part of routine cervical cancer screening. 1

Current Recommendations for Cervical Cancer Screening in 25-Year-Olds

The 2021 CDC Sexually Transmitted Infections Treatment Guidelines explicitly state that HPV testing should not be performed in persons younger than 25 years as part of routine cervical cancer screening 1. This recommendation applies to all HPV testing methods, including mRNA-based tests that detect viral messenger RNA.

The American Cancer Society (ACS) updated their guidelines in 2020 to recommend:

1. Initiation of cervical cancer screening at age 25 (changed from age 21)
2. Primary HPV testing every 5 years as the preferred screening method for those aged 25-65 years
3. Cytology alone every 3 years or cotesting (HPV plus cytology) every 5 years as acceptable alternatives where primary HPV testing is not available 1

Rationale Behind Age Recommendations

Several key factors support not performing HPV testing, including mRNA testing, in those under 25 years:

• Low disease burden: The incidence of cervical cancer in individuals under 25 years is very low 1
• High transient infection rate: Young people have a high rate of transient HPV infections that typically clear without causing significant disease 1
• Potential harms: Early testing leads to unnecessary colposcopies, biopsies, and potential treatment of lesions that would likely regress naturally 1
• Psychological impact: False positive results can cause unnecessary anxiety
• Obstetrical risks: Cervical excisional procedures resulting from over-detection may increase risk of adverse obstetrical outcomes 1

Types of HPV Tests Available

Several FDA-cleared HPV tests are available in the United States:

• DNA-based tests: Detect viral DNA (e.g., Cobas 4800 HPV test, Hybrid Capture 2)
• mRNA-based tests: Detect viral messenger RNA (e.g., APTIMA HR HPV)

Both test types are only FDA-cleared for use with cervical specimens, not oral or anal specimens 1. Some tests are approved for primary screening while others are only approved for use in conjunction with cytology or for triage of abnormal cytology results.

Performance of HPV mRNA Testing

Research has shown that HPV mRNA testing has:

• Higher specificity than DNA testing for high-grade lesions (72.7% vs 56.2%) 2
• Higher positive predictive value than DNA testing (59.3% vs 49.0%) 2
• Comparable sensitivity to cytology but higher specificity in post-colposcopy follow-up 3

However, these potential advantages do not override the recommendation against HPV testing in those under 25 years.

Appropriate Cervical Cancer Screening for 25-Year-Olds

For 25-year-olds specifically:

1. Begin screening at age 25 with primary HPV testing (preferred), cytology alone, or cotesting 1
2. Do not use HPV testing (DNA or mRNA) for:
   • Deciding whether to vaccinate against HPV
   • Testing for low-risk HPV types
   • Managing genital warts
   • Testing oral or anal specimens 1

Common Pitfalls to Avoid

• Don't start HPV testing too early: Starting before age 25 leads to detection of transient infections and unnecessary procedures
• Don't use unapproved testing methods: Self-collection for HPV testing is not FDA-cleared or recommended by U.S. medical organizations 1
• Don't confuse screening and diagnostic testing: HPV testing in young people may be appropriate in specific diagnostic scenarios, but not for routine screening
• Don't use HPV mRNA testing in urine samples: Research shows this approach has suboptimal sensitivity (31.5%) for cervical cancer screening 4

In conclusion, while HPV mRNA testing has potential advantages in certain clinical scenarios, it should not be used for routine cervical cancer screening in 25-year-olds. The appropriate approach is to begin cervical cancer screening at age 25 using primary HPV testing (preferred) or cytology-based methods.