Human papillomavirus (HPV) 16 E6 gene mutation is considered an important genetic change in cervical lesion progression. To explore the possible association of specific HPV16 E6 sequence variations with the development of invasive cervical squamous cell carcinoma (SCC) in young women, we examined the distribution of HPV16 E6 variants in a Chinese cervical SCC population and analyzed the difference between younger patients (≤35 years, n = 50) and older ones (>35ys, n = 71). Human papillomavirus type 16 E6 DNA was amplified by polymerase chain reaction and sequenced by Sanger fluorescent dye dideoxy-termination method. Analysis revealed that the most frequently found variation in this Chinese population was the EV (As) lineage (65.45%). In addition, the EV (As) lineage seems more common and uniform in younger patients than other lineages, and it may be associated with early age at diagnosis of cervical SCC in young women.