HPV Predominantly Infects Cells in the Basal Layer
HPV specifically targets and infects the basal keratinocytes of stratified squamous epithelium, not the stratum spinosum. This is the fundamental pattern of HPV infection across all tissue types.
Mechanism of Basal Layer Infection
The virus must access the basal epidermal layer to establish infection, where it initially replicates and maintains its genome as episomes in these proliferating cells. 1 The British Association of Dermatologists guidelines explicitly state that "the development of epidermal thickening and hyperkeratinization occurs following infection at the basal layer and clonal proliferation, which eventually results in a visible wart, weeks or even months later." 1
Why the Basal Layer is the Target
HPV specifically infects basal keratinocytes because these are the only cells in stratified squamous epithelium that are actively dividing and progressing through the cell cycle. 1
The overlying stratified squamous epithelium normally protects the basal keratinocytes, requiring microabrasions (such as from sexual intercourse or minor trauma) to allow viral access to these underlying target cells. 1
Cell cycle progression through mitosis is absolutely required for HPV infection to be established—the virus cannot successfully infect cells that are not progressing through the cell cycle. 2
The Differentiation-Dependent Viral Life Cycle
Once basal layer infection is established, the viral life cycle follows a specific pattern tied to epithelial differentiation:
In infected basal cells, viral DNA is maintained at low copy numbers and replicates in synchrony with host cell DNA. 3, 4
As infected cells migrate upward and differentiate into suprabasal layers (including stratum spinosum and beyond), vegetative viral replication and late gene expression are activated. 3, 4
Progeny virion production occurs only in the highly differentiated superficial cells, not in the basal layer where initial infection occurs. 3, 4
Clinical Significance
This basal layer tropism explains several key clinical features:
In tonsillar tissue, basal keratinocytes are naturally exposed in the base of tonsillar crypts, which explains why oropharyngeal HPV infection and cancer occur preferentially at these sites. 1
The requirement for basal layer access explains why HPV transmission requires some degree of epithelial disruption or access to naturally exposed basal cells. 1
Understanding that infection begins in the basal layer but viral replication completes in differentiated layers explains the weeks-to-months delay between infection and visible wart formation. 1
Common Pitfall to Avoid
Do not confuse the site of initial infection (basal layer) with the site of viral replication and virion production (suprabasal differentiated layers including stratum spinosum). The question asks about the pattern of infection, which refers to where the virus initially establishes itself—definitively the basal layer. 1, 3, 4