Objective: To identify knowledge and beliefs about the human papillomavirus (HPV) among students in a residential academic institution, including perceptions of safety of the HPV vaccine, perceptions of cancer correlation with HPV, and independence/interdependence in health decision-making. Design: A qualitative study was used. Setting: Participants were recruited from a small private US university. Methods: In-depth, semi-structured interviews. Results: Study findings highlight the need for improved communication about sex and general preventive health care between young adults, their parents and health providers, including the campus health services centre. Findings point to the importance of appropriate health care messaging at the time of the HPV vaccine (if given in adolescence) throughout college. While mothers played a crucial part in helping young adults make sense of health and health care decisions, self-reliance and self-protection were strong drivers of decision-making. Conclusion: As college students progress from dependent child to independent adult, they shift from reliance on others, especially mothers, for health guidance to an emerging self-reliance and self-protective stance. Central to this experience is navigating health decisions by using information from one's childhood and integrating new knowledge as one emerges into adulthood. College health care providers and related disciplinary faculty have the opportunity to support students during this transition.