Based on improvements in HPV detection technology, it appears that an almost 100% HPV association is reached for cervical cancer, as demonstrated in an accompanying paper in this issue of the Journal. Factors which may explain the rare cases in which no HPV DNA is detectable include: improper sampling; disruption of HPV by integration events; the existence of still unidentified HPVs; sensitivity of the method; and the mechanism of transformation. Finally, epidemiological studies identifying HPV independent risk factors are necessary to answer the question of whether HPV independent pathways exist for cervical carcinogenesis.