What are the other human papillomavirus (HPV) related malignancies aside from cervical cancer?

HPV-Related Malignancies Beyond Cervical Cancer

HPV causes multiple cancers beyond cervical cancer, including vaginal, vulvar, anal, penile, and oropharyngeal malignancies, with HPV types 16 and 18 responsible for the majority of these HPV-attributable cancers. 1

Anogenital Cancers

Vaginal Cancer

• HPV is associated with the majority of vaginal cancers and vaginal intraepithelial neoplasia III (VaIN III), with HPV 16 being the most common type 1
• Approximately 1,070 cases occur annually in the United States (incidence rate: 0.7 per 100,000 females) 1
• The median age at diagnosis is 69 years, significantly higher than cervical cancer 1
• HPV DNA is detected in a high proportion of vaginal cancers, though the exact percentage varies by study 2

Vulvar Cancer

• HPV is associated with approximately 40-50% of vulvar squamous cell cancers 3, 1
• HPV types 16 or 18 are detected in 76% of VIN 2/3 and 42% of vulvar carcinoma samples 1
• Approximately 3,507-3,870 cases occur annually in the United States (incidence rate: 2.2 per 100,000 females) 3, 1
• HPV-associated vulvar cancer tends to occur in younger women and may be preceded by vulvar intraepithelial neoplasia (VIN) 1

Anal Cancer

• HPV is associated with approximately 90% of anal squamous cell cancers, representing the highest HPV attribution rate among anogenital cancers 1, 4
• Approximately 4,000 cases are diagnosed annually in the United States (620 deaths) 3
• Anal cancer is more common in women (1.6 per 100,000) than in men (1.3 per 100,000) 1
• HPV16 accounts for around 80% of HPV DNA-positive anal cancers 2
• Anal intraepithelial neoplasia (AIN) is recognized as a precursor lesion 1
• High-risk populations include women with high-grade cervical lesions, men who have sex with men, and persons with HIV infection 1

Penile Cancer

• Up to 50% of penile cancer cases are linked to HPV infection, with HPV type 16 being the most frequent 1, 5
• Penile cancers are now classified as HPV-associated or HPV-independent based on the 2022 WHO classification 1, 5
• The HPV attribution is lower than anal cancer but still clinically significant 2

Head and Neck Cancers

Oropharyngeal Cancer

• HPV is responsible for a significant proportion (63-72%) of oropharyngeal cancers 1
• Oropharyngeal cancers are more common in males (72%) than females (63%) 1
• Approximately 80-90% of anal cancers are caused by either HPV16 or HPV18 3
• Oropharyngeal cancer precursors have yet to be identified, and there are currently no routine screening tests recommended 4

Other HPV-Related Conditions

Anogenital Warts

• Over 500,000 new cases of anogenital warts are diagnosed annually in the United States 3
• About 90% are caused by HPV types 6 or 11 (low-risk types) 3
• Approximately 10% of men and women will develop anogenital warts at some point in their lives 3

Juvenile Laryngeal Papillomatosis

• Occurs in about 1 in 200,000 children under age 18 years, most before age 4 years 3
• HPV types 6 and 11 are most commonly associated with this condition 3
• Characterized by recurrent benign tumors that may lead to respiratory obstruction and require repeated surgical removal 3

Risk Factors Across All HPV-Related Cancers

• Persistent infection with high-risk HPV types is necessary for progression to cancer 1
• Common risk factors include multiple sexual partners, current tobacco use, immune deficiency, and co-infection with other sexually transmitted diseases 1
• Immunosuppression significantly increases the risk, with solid organ transplant recipients showing elevated standardized incidence ratios for vulvar and vaginal cancers 3, 1

Critical Clinical Considerations

Prevention

• HPV vaccination can prevent up to 90% of cervical cancers and significantly reduce the risk of other HPV-related cancers 1
• Current vaccination is recommended at age 11 or 12 for all genders with catch-up vaccination up to age 26 4

Screening Limitations

• Unlike cervical cancer, there are no standardized screening recommendations for most other HPV-related cancers, making prevention through vaccination particularly important 1, 5
• Examination of the anal canal is best performed by trained clinicians using high-resolution anoscopy, though optimal screening remains unclear 4
• No routine screening exists for oropharyngeal cancer 4

Common Pitfall

• Do not assume all gynecologic cancers are HPV-related; uterine (endometrial) cancer shows minimal or no increased risk related to HPV infection, with standardized incidence ratios ranging from only 0.9 to 2.1 6