Concept of the Existence of Human Papillomavirus (HPV) DNA in Histologically Normal Squamous Epithelium of the Genital Tract Should be Re‐Evaluated

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Abstract
Because of the crucial importance of guiding current thinking in the field of HPV epidemiology, the concept of the existence of HPV DNA in histologically normal squamous epithelium was re-evaluated. A series of 102 randomly collected cervical punch biopsies, previously proved to contain the DNA of HPV types 6, 11, 16, 18, 31 or 33 by in situ hybridization were subjected to analysis for the localization of HPV DNA, i.e., whether found in the normal epithelium or at the lesion site only. This material consisted of a representative series of flat, endophytic and papillary HPV lesions with all histological grades from HPV-NCIN to HPV-CIN III, and the six HPV types in the same proportions as they occur in non-selected series of HPV lesions. Weak signals of HPV DNA were found in the basal cells in 6/102 (5.8%) of the biopsies. HPV DNA was constantly present in the parabasal cells in 25/102 (25.4%), in the intermediate cell layers in (98/102, 96%), and in the superficial cells of all 102 lesions. Noteworthy was the constant failure to reveal even weak signals of HPV DNA (of any of the six types) in histologically normal squamous epithelium of any of the 87 lesions, where such an epithelium was detectable. The present findings confirm our previous ''impression'' that HPV DNA rarely if ever appears in the histologically normal squamous (or columnar) epithelium in the genital tract, when analysed using the in situ hybridization. Thus, great care should be exercised in interpreting results that suggests the discovery of HPV DNA in normal genital tract epithelium, unless based on firm documentation by in situ hybridization.