HPV‑16: Predominant High‑Risk Genotype Across HPV‑Associated Malignancies

Epidemiology of Cervical Cancer

HPV‑16 is responsible for 50‑60 % of invasive squamous‑cell cervical carcinomas worldwide, making it the most prevalent genotype in cervical cancer cases. 1, 2, 3
HPV‑18 is the second‑most common genotype, accounting for 10‑15 % of cervical cancers. 2, 3, 4
In cervical adenocarcinoma, HPV‑16 accounts for approximately 40 % of cases, while HPV‑18 is detected in about 30 % of cases. 2, 5

HPV‑16 has the highest propensity to establish a persistent infection compared with other high‑risk types. 5
When persistence occurs, HPV‑16 shows the greatest probability of progression to cervical intra‑epithelial neoplasia grade 3 (CIN 3). 2
HPV‑16 is the most frequently identified genotype in high‑grade precancerous lesions (CIN 3). 3

Combined with HPV‑18, HPV‑16 accounts for more than 80 % of penile, anal, oropharyngeal, and other head‑and‑neck cancers in men. 6
In oropharyngeal cancer, HPV‑16 is present in 70 % of HPV‑positive cases. 6
Among immunosuppressed individuals, HPV‑16 is detected in over 90 % of HPV‑related vulvar cancers. 7, 8, 9

The 2025 Taiwan national guidelines identify HPV‑16 and HPV‑18 as the most carcinogenic genotypes, together responsible for 71 % of HPV‑associated cancers globally, with HPV‑16 being the dominant contributor. 6
Extended genotyping protocols categorize HPV‑16 and HPV‑18 into the highest oncogenic‑risk group. 10

Women who test positive for HPV‑16 but have negative cytology should be referred immediately for colposcopy when partial genotyping is used. 10
Persistent HPV‑16 infection warrants more aggressive surveillance because of its higher likelihood of progression to high‑grade disease. 3, 5

Approximately 15 carcinogenic HPV types together cause virtually all cervical cancers worldwide. 2, 3
The remaining high‑risk genotypes (including 18, 31, 33, 35, 45, 52, and 58) account for the other 30‑40 % of cases, but none approach the individual cancer burden of HPV‑16. 1, 6

HPV‑16 and HPV‑18 together cause roughly 70 % of all cervical cancers worldwide; HPV‑16 alone accounts for 50‑60 % and HPV‑18 for 10‑15 % of cases. 11

In squamous cell carcinoma (which represents about 75‑80 % of cervical cancers), HPV‑16 and HPV‑18 are detected in approximately 68 % of tumors. 12, 13, 14, 15
Within squamous cell carcinoma, HPV‑16 alone is present in 53‑76.7 % of cases. 12
HPV‑18 contributes to 7.8‑15 % of squamous cell carcinoma cases. 12
In adenocarcinoma (comprising about 20‑25 % of cervical cancers), HPV‑16 and HPV‑18 together account for approximately 83 % of tumors. 12, 13, 14, 15

HPV‑18 is disproportionately represented in glandular (adenocarcinoma) cancers, being found in ≈32 % of such tumors versus ≈8 % in squamous cell carcinoma. 11

Among immunosuppressed individuals, HPV‑16 is detected in over 90 % of HPV‑related vulvar cancers. 16
The type distribution of HPV in vaginal cancers mirrors that observed in cervical cancer. 16

Across all anatomical sites, HPV‑16 and HPV‑18 together are responsible for about 70 % of all HPV‑related cancers worldwide. 17, 18
The remaining 30 % of cervical cancers are attributable to roughly 10 other high‑risk HPV types (including 31, 33, 35, 45, 51, 52, 58, 59). 16

Current HPV vaccines (bivalent, quadrivalent, and nonavalent) all provide protection against HPV‑16 and HPV‑18. 17, 18, 19
Vaccination programs that target HPV‑16 and HPV‑18 are projected to prevent more than 70 % of cervical cancers. 17, 19
The 9‑valent vaccine additionally covers five high‑risk types (31, 33, 45, 52, 58), which together account for an extra 14 % of HPV‑related cancers in women and 4 % in men. 17