The study aimed to improve the amplification of genital human papillomaviruses (HPVs) by redesigning the MY09/11 primer system. The original MY09/11 primers, which were designed to amplify a broad spectrum of HPV genotypes, showed varying levels of sensitivity among different HPV types. The new PGMY09/11 primer system was developed to increase the sensitivity of amplification across the type spectrum. The PGMY09/11 primers were designed to be 100% conserved with the target sequences, using multiple oligonucleotide sequences to accommodate sequence heterogeneity. The performance of the PGMY09/11 system was evaluated using 262 cervicovaginal lavage specimens, showing a 91.5% overall agreement with the MY09/11 system (kappa = 0.83; P < 0.001). The PGMY09/11 system detected an additional 20 HPV-positive specimens, with a prevalence of 62.8% compared to 55.1% with the MY09/11 system. The new system detected HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and 87 at least 25% more often. The PGMY09/11 primer system offers improved sensitivity and specificity in HPV detection, particularly in samples with multiple HPV types, and is useful for assessing the natural history of HPV infections.The study aimed to improve the amplification of genital human papillomaviruses (HPVs) by redesigning the MY09/11 primer system. The original MY09/11 primers, which were designed to amplify a broad spectrum of HPV genotypes, showed varying levels of sensitivity among different HPV types. The new PGMY09/11 primer system was developed to increase the sensitivity of amplification across the type spectrum. The PGMY09/11 primers were designed to be 100% conserved with the target sequences, using multiple oligonucleotide sequences to accommodate sequence heterogeneity. The performance of the PGMY09/11 system was evaluated using 262 cervicovaginal lavage specimens, showing a 91.5% overall agreement with the MY09/11 system (kappa = 0.83; P < 0.001). The PGMY09/11 system detected an additional 20 HPV-positive specimens, with a prevalence of 62.8% compared to 55.1% with the MY09/11 system. The new system detected HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and 87 at least 25% more often. The PGMY09/11 primer system offers improved sensitivity and specificity in HPV detection, particularly in samples with multiple HPV types, and is useful for assessing the natural history of HPV infections.