HPV infection and telomerase induction. Telomerase, and its rate determining catalytic subunit, hTERT, is normally not expressed in somatic cells. With a HR HPV infection, E6 and E7 activate the hTERT gene. With disease progression, hTERT activation and telomerase activity increases (demonstrated by darker, larger arrows), and the expression of HR E6 and E7 also increases with the integration of HPV DNA into the host cell chromosomal DNA or loss of E2 regulation. LGSIL (low-grade squamous intraepithelial lesion) is typical for an active HPV infection. HGSIL (high-grade squamous intraepithelial lesion) is typical for a HR HPV infection with worsening cytologic changes and parallel greater histologic involvement, with multiple layers of the stratified squamous epithelium. CIN2/3 (cervical intraepithelial neoplasia 2 or 3) shows histologic changes due to an active HPV infection that involved most (2) or all (3) of the stratified squamous epithelium. Carcinoma in situ is the full thickness involvement of stratified squamous epithelium without breakdown of the basement membrane.