With great progress in HPV assay development over the past 5-7 years, and especially PCR based assays, BGI Shenzhen (the world’s largest genomic sequencing facility) asked the question if sequencing technology can move the science and the POI screening paradigm even further. With the new bench-top next generation sequencing instruments currently available such as the Ion Torrent Personal Genome Machine (PGM, Life Technologies, Carlsbad CA, USA ) and MiSeq (Illumina, San Diego, CA, USA), fast progress in DNA sequencing technology has allowed a substantial reduction in costs along with improved accuracy and throughput.  BGI in collaboration with POI believed it would be possible that by using next generation sequencing (NGS) technology, we could drive the costs lower and the applicability even wider due to the cost and transportability of the latest in NGS technology.To achieve this goal, we designed a high throughput HPV genotyping assay based on multiplex PCR and next generation sequencing. We used PGM and MiSeq, and optimized the HPV positive cutoff of this new assay and then validated the assay on population based self-collected samples from SHENCCAST II. The result was a high throughput, highly sensitive, low cost per assay. The sensitivity for ≥CIN 2 and ≥CIN 3 of the self-sampling specimens tested by the new NGS HR-HPV genotyping assay (SEQHPV) was similar to that of direct sampling specimens tested by HC2 (p>0.05)，but the specificity for ≥CIN 2 and ≥CIN 3 of  SEQHPV was significantly higher  than HC2 (p<0.01).  This work “Development and validation of a new HPV genotyping assay based on next generation sequencing”, was  Accepted November 2013, for publication in the Am J. Clinical Pathology. We  hope to continue this work to further improve assay specificity by incorporating the detection of viral methylation.