Overexpression of p16 can result from disruption of the negative feedback loop that normally operates among p16, cyclin-dependent kinases, cyclins, and phosphorylation of retinoblastoma protein; several causes—including human papillomavirus infection—can disrupt this loop [24], and such disruption may facilitate cell cycle progression and make cells more susceptible to the carcinogens in cigarettes and cigarette smoke. The gene discussed is CDKN2A; the disease is human papilloma virus infection.