What are the most critical Human Papillomavirus (HPV) genotypes to be aware of?

Critical HPV Genotypes to Know

HPV types 16 and 18 are the two most critical genotypes, causing approximately 70% of all cervical cancers worldwide, with HPV-16 alone accounting for 55-60% of cases and being the single most carcinogenic type. 1

High-Risk (Oncogenic) HPV Types

The "Big Two" - Highest Priority

• HPV-16: The most carcinogenic genotype, responsible for 55-60% of all cervical cancers 1
• HPV-18: The second most carcinogenic type, causing 10-15% of cervical cancers 1
• Together, HPV-16 and 18 account for approximately 68% of squamous cell cancers but 83% of adenocarcinomas 2
• HPV-18 disproportionately causes glandular cancers (adenocarcinoma and adenosquamous carcinoma) at 32% versus only 8% for squamous cell carcinoma 1

Additional High-Risk Types - Secondary Priority

The following high-risk types collectively cause the remaining 25-35% of cervical cancers: 1

• HPV-31,33,45,52,58: These five types, when combined with HPV-16 and 18, account for approximately 87-91% of all cervical cancers 1, 3
• Other high-risk types: HPV-35,39,51,56,59,68,69,73, and 82 1
• High-risk HPV types are detected in 99% of cervical cancers 1

Regional Variations Worth Noting

• HPV-52 and 58 are particularly common in Asian populations, with HPV-52 being the second most common type in some Chinese studies (2.86% infection rate) 3
• In India, HPV-16,18,31,33, and 45 were detected in 87.1% of cervical cancer cases 4

Low-Risk HPV Types

Genital Warts and Benign Lesions

• HPV-6 and 11: Cause approximately 90% of genital warts and recurrent respiratory papillomatosis 1
• These types cause benign or low-grade cervical cell changes but are not carcinogenic 1

Clinical Risk Stratification

Highest Risk for Progression

• HPV-16 persistence: Women with one-year or two-year persistent HPV-16 infection have a 20-30% risk of developing CIN3+ over 5 years 1
• Among cytology-negative women aged ≥30 years, CIN3 was identified in 21% with HPV-16 and 18% with HPV-18 during 10 years of follow-up, compared to only 1.5% for other high-risk types 1

Moderate Risk Types

• HPV-31,33,45,52, and 58 have intermediate carcinogenic potential 1, 5
• These types become increasingly important as HPV-16/18 vaccination coverage increases 6

Practical Implications for Screening and Management

HPV Testing Algorithms

• Only test for high-risk (oncogenic) HPV types - testing for low-risk types has no clinical utility in cervical cancer screening 1
• For women ≥30 years with negative cytology but positive HPV: repeat testing at 12 months is preferred 1
• HPV-16/18 genotyping allows risk stratification: women with these types should proceed directly to colposcopy, while those with other high-risk types can be followed with repeat testing 1

Vaccination Coverage

• Bivalent vaccines: Protect against HPV-16 and 18 1, 5
• Quadrivalent vaccines: Protect against HPV-6,11,16, and 18 1
• Nonavalent vaccine: Covers HPV-6,11,16,18,31,33,45,52, and 58 1, 5
• Current vaccines targeting HPV-16 and 18 have the potential to prevent over 70% of cervical cancers globally 2, 4

Common Pitfalls to Avoid

• Don't assume all HPV infections lead to cancer: Approximately 90% of HPV infections are transient and clear within 1-2 years 1, 7
• Don't ignore non-16/18 types: As vaccination coverage increases, the relative proportion of cancers caused by other high-risk types will increase 6
• Don't overlook HPV-18 in adenocarcinomas: This type has a particular predilection for glandular lesions and requires specific attention 1
• Don't test for low-risk HPV types in cancer screening contexts - this provides no actionable clinical information 1