Can actinic keratosis be caused by Human Papillomavirus (HPV)?

Actinic Keratosis and HPV: Examining the Relationship

No, actinic keratosis is not primarily caused by HPV, but rather by chronic UV exposure, although HPV may play a role as a cofactor in some cases and is associated with increased recurrence rates.

Primary Etiology of Actinic Keratosis

• Actinic keratoses (AKs) are keratotic lesions occurring on chronically light-exposed adult skin, representing focal areas of abnormal keratinocyte proliferation and differentiation 1
• The primary cause of AKs is chronic exposure to ultraviolet (UV) radiation, with UVB-specific p53 mutations demonstrated in AKs providing molecular evidence supporting sunlight's role 1
• AKs occur predominantly on chronically sun-exposed skin such as the face and dorsa of hands, particularly in fair-skinned individuals 1
• They present as discrete, sometimes confluent, patches of erythema and scaling on predominantly sun-exposed skin, usually in middle-aged and elderly individuals 1

Evidence for HPV Association with Actinic Keratosis

• Research has shown that HPV DNA can be detected in 47% of AK lesions compared to 37% in normal skin, suggesting a possible association 2
• The highest prevalence of cutaneous HPV types is found in eyebrow hairs (84%) of AK patients, which may serve as a reservoir for infection 2
• HPV positivity has been associated with AK recurrence after treatment, with one study showing that AK lesions recurred in all HPV-positive patients after laser treatment (within 45-60 days) while disappearing in HPV-negative ones 3
• Multiple HPV types, particularly from beta and gamma genera, have been identified in AK lesions, with gamma-1 species (e.g., HPV4) appearing to be enriched in AK versus healthy skin 4

HPV as a Cofactor Rather Than Primary Cause

• While HPV DNA is found in AK lesions, the primary etiology of AKs remains chronic UV exposure 1
• HPV may function as a cofactor that influences the severity and recurrence of AK lesions rather than being the primary causative agent 3
• Cell-cycle proteins (p53, p21, PCNA, Ki-67) are overexpressed in AKs, and HPV may interact with these pathways to support its own DNA replication while contributing to cell proliferation 5
• The presence of HPV L1 seropositivity increases with lesion severity from normal skin to AK to squamous cell carcinoma (SCC), suggesting a potential role in disease progression 6

Clinical Implications

• When evaluating patients with AKs, the primary focus should be on assessing sun damage and UV exposure history 1
• Treatment decisions for AKs should be based on factors such as number of lesions, thickness, location, and patient characteristics rather than HPV status 1
• Persistent or recurrent AKs following appropriate treatment may warrant consideration of HPV testing, as HPV positivity has been associated with higher recurrence rates 3
• The presence of HPV in AKs may have implications for long-term management and follow-up, particularly regarding the risk of progression to SCC 6

Distinguishing from HPV-Related Lesions

• It's important to distinguish AKs from true HPV-induced lesions such as verruca vulgaris, condyloma acuminatum, and squamous papillomas, which have distinct clinical and histological features 1
• Unlike typical HPV-induced lesions, AKs show epithelial dysplasia as their cardinal histological feature 1
• HPV-induced lesions like verruca vulgaris typically show koilocytes and a heavy granular layer histologically, features not characteristic of AKs 1
• While HPV may be detected in AKs, the lesions do not display the typical clinical appearance of viral warts 1

In conclusion, while HPV may play a role as a cofactor in some cases of actinic keratosis and is associated with increased recurrence rates, the primary cause of AKs remains chronic UV exposure. The relationship between HPV and AKs requires further research to fully elucidate the clinical significance and potential therapeutic implications.