Our study does not make that assumption; it focuses on demonstrating the presence and evolutionary authenticity of HPV16 in ancient humans, not on reconstructing clinical phenotype or tissue localization.

We are dealing with viral lineages that are ~5,300 and ~45,000 years old. It cannot be assumed a priori that their tropism, pathogenicity, integration dynamics, or systemic behavior were identical to those of modern HPV16.

We also cannot exclude the possibility of a subclinical neoplastic focus at the time of death. Integrated HPV16 can generate circulating viral DNA even in the absence of clinically evident cancer, which limits anatomical or pathological inference.

Detection of HPV16 does not necessarily imply active mucosal epithelial infection at the time of death. Viral integration can occur. Integrated HPV DNA may persist in different descendant cell types, making it impossible to reconstruct the original tissue of infection from aDNA data alone.