Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus of the Papillomaviridae family.
To date, over 200 genotypes have been identified, classified by DNA sequence homology in the viral L1 gene. These genotypes exhibit distinct tissue tropisms—cutaneous or mucosal—and variable oncogenic potential. Understanding HPV classification guides clinical management, screening strategies, and preventive measures (World Health Organization, 2023).
1. Cutaneous versus Mucosal HPV
- Cutaneous HPVs infect keratinized epidermis, producing common (verruca vulgaris), plantar, and flat warts. Predominant cutaneous types include HPV-1, -2, -3, -4, and -10.
- Mucosal HPVs target non-keratinized squamous epithelium of the anogenital tract and oropharynx. Approximately 40 mucosal genotypes exist, subdivided by their clinical outcomes into low-risk (LR) and high-risk (HR) categories (World Health Organization, 2023).
2. Low-Risk HPV Genotypes
Low-risk HPVs rarely lead to malignancy; they induce benign proliferations:
- HPV-6 and HPV-11
- Responsible for over 90 % of anogenital warts (condylomata acuminata).
- Also cause recurrent respiratory papillomatosis, characterized by airway-obstructing papillomas (National Cancer Institute, 2022).
- Other LR types (e.g., HPV-40, -42, -43, -44, -54) can produce genital warts less frequently.
Although non-oncogenic, LR infections may recur and require repeated treatment.
3. High-Risk HPV Genotypes
High-risk HPVs encode E6 and E7 oncoproteins that inactivate p53 and retinoblastoma (pRb) tumor suppressors, promoting cellular immortalization and carcinogenesis if infection persists (Centers for Disease Control and Prevention, 2024).
| Genotype | Approximate Contribution to Cervical Cancer |
| HPV-16 | ≈ 60 % of cervical cancers; also prominent in oropharyngeal carcinomas |
| HPV-18 | ≈ 10–15 % of cervical cancers; overrepresented in adenocarcinomas |
| HPV-31, -33, -45 | Together account for ≈ 10 % of cases |
| HPV-52, -58 | Regionally significant; included in nonavalent vaccines |
| Others (e.g., 35, 39, 51, 56, 59, 68) | Less frequent but classified as oncogenic |
Persistent HR infection increases risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) and invasive carcinoma over 10–20 years (National Cancer Institute, 2022).
4. Implications for Screening and Prevention
- Genotype-Specific Testing
- HPV DNA tests detect pooled HR types and can specifically identify HPV-16/18, enabling risk stratification and timely referral to colposcopy (World Health Organization, 2023).
- Prophylactic Vaccination
- Bivalent (HPV-16/18), quadrivalent (adds HPV-6/11), and nonavalent (adds HPV-31/33/45/52/58) vaccines can prevent up to 90 % of cervical cancers and most anogenital warts when administered before HPV exposure (Centers for Disease Control and Prevention, 2024).
- Surveillance and Epidemiology
- Ongoing monitoring of genotype prevalence post-vaccination informs on herd immunity effects and potential genotype replacement, guiding updates to vaccine composition (World Health Organization, 2023).
- Management of Lesions
- Benign lesions (LR types): treated with cryotherapy, surgical excision, or topical agents (e.g., imiquimod).
- Precancerous lesions (HR types, CIN 2/3): managed via excisional procedures such as loop electrosurgical excision procedure (LEEP) or cold-knife conization to prevent progression (National Cancer Institute, 2022).
HPV genotype classification by tropism and oncogenic risk is foundational to effective public health strategies. Cutaneous types cause benign warts; LR mucosal types induce condylomas and respiratory papillomas; HR types drive cervical and other anogenital/oropharyngeal cancers. Genotype-specific diagnostics and widespread vaccination targeting the most oncogenic types are essential tools to reduce HPV-associated disease burden globally.
References
Centers for Disease Control and Prevention. (2024). HPV and cancer. https://www.cdc.gov/hpv/about/cancers-caused-byhpv.html?CDC_AAref_Val=https://www.cdc.gov/hpv/parents/cancer.html
National Cancer Institute. (2022). HPV and cancer: HPV infection and cervical cancer. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-fact-sheet
World Health Organization. (2023). Human papillomavirus (HPV) and cervical cancer. https://www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer