The availability of vaccines against certain HPV types and the development of broad spectrum genotyping methods have increased interest in co-infections with different HPV types. In the present study, the prevalence and type-specific composition of multiple HPV infections were investigated in a routine cervical screening population in West Germany both at a cross-sectional level and longitudinally. Four hundred eighty-nine out of 8,090 women were diagnosed with multiple HPV infections once or repeatedly. During the 7.5-year study period, the cumulative prevalence of HPV co-infections was 15.3% in contrast to the cross-sectional prevalence of 3.8% at single visits. The overall cumulative prevalence within the cohort of all women screened was 6.9%. Using consensus PCR with sequencing and type-specific PCRs, two to three HPV types were detected simultaneously, whereas broad spectrum methods detected up to seven different genotypes in one sample. Nevertheless, the most common pattern of co-infection occurred with two to three HPV types irrespective of the age of the patient, cytology and histology of the lesions and the method used. The most common genotypes detected were HPV 16, 31, 53, 51, 52, and 66, and the most common pattern of co-infection was double infection with HPV 16 and 31. These results show that rates and patterns of multiple HPV infections are largely dependent on the methodology used and the time interval between tests. Given the significance of HPV vaccination and its expected influence on immunized populations, it is essential to gain additional insights into the natural course and pathogenic effect of multiple HPV infection longitudinally.

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