Meta-analysis of overall HPV prevalence
A total of 10
058 ICC cases from the 85 identified studies were included in this meta-analysis of HPV prevalence (). A majority of cases came from studies performed in Asia (31%) and Europe (33%), with African studies representing the smallest proportion of cases (6%). HPV prevalence was reported stratified by histological type for 73% of the cases: 5825 SCC cases and 1508 ADC cases. In total, 12 studies included only SCC and seven studies included only ADC.
Region- and histology-specific distribution of included studies and ICC cases
Adjusted overall HPV prevalence ranged from 79.3% in Asia to 88.1% in North America and Australia, but did not differ significantly between regions (). HPV DNA was significantly less likely to be detected in ADC (76.5%) than in SCC (87.3%) (P<0.001). DNA detection in ICC of unspecified histology (89.2%) was similar to that in SCC.
Prevalence of HPV by region, histological type, HPV DNA specimen and PCR primers used
Adjusted HPV prevalence was significantly higher from studies testing both cells and biopsies for HPV DNA (92.5%) than from studies testing either cervical exfoliated cells (78.9%) or fixed biopsies (83.3%) only. For PCR primers, highest HPV prevalence was obtained in studies using SPF10 primers (97.2%) and the lowest in studies using type-specific PCR (TS-PCR) only (74.7%). Adjusted overall HPV prevalence varied between 77.8 and 90.1% for other primer sets, but these differences were not statistically significant.
Meta-analysis of HPV type-specific prevalence
Owing to their similar overall and type-specific HPV prevalence, ICC of unspecified histology were combined with SCC for comparison of HPV type-specific prevalence by histological type (). The most common HPV types identified were, in order of decreasing prevalence, HPV16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. Other HPV types were detected in no more than 0.2% of ICC cases. There was considerable variation in HPV-specific prevalence between SCC and ADC. HPV16 was identified more often in SCC (55.2%) than in ADC (31.3%) (P<0.001). The same was found for the HPV16 phylogenetically related types 31, 33, 52 and 58 (P<0.001), but not 35. Conversely, HPV18 was more prevalent in ADC (37.7%) than in SCC (12.3%) (P<0.001). The HPV18 phylogenetically related type 45 was also more prevalent in ADC (5.8%) than in SCC (3.4%) (P=0.04).
Figure 1 Type-specific prevalence of HPV in 10058 worldwide cases of invasive cervical cancer by histological type.
Comparison of HPV-specific prevalence in SCC by region is shown in . In SCC, HPV16 was the predominant type in all regions studied, varying from 45.9% in Asia to 62.6% in North America and Australia. HPV18 was found consistently in 10–14% of SCC cases. In most regions, HPV45 (2–8%), 31 (2–7%) and 33 (3–5%) were the most prevalent types in SCC after types 16 and 18. In cases from Africa, the prevalence of HPV45 (8.0%) was more than twice that of either 31 (2.7%) or 33 (3.2%). In cases from Asia, HPV58 (5.8%) and 52 (4.4%) were found more commonly than HPV45, 31 and 33. Other HPV types varied considerably in their prevalence from region to region, but accounted for no more than 2% of ICC cases from any region.
Type-specific prevalence of HPV in 8550 cases of squamous cell and unspecified cervical carcinoma by region.
Sufficient ADC-specific data existed for the comparison of HPV-specific prevalence across Asia, Europe and North America and Australia (). HPV18 was the predominant type (37.7%), found consistently in 37–41% of ADC cases in these regions, with HPV16 accounting for a smaller proportion (26–36%). HPV45 was the third most prevalent in each region, present in 5–7% of ADC cases vs only in 2–4% of SCC cases from these regions. The HPV16 phylogenetically related types 31, 33, 52 and 58 (but not 35) were all less prevalent in ADC cases than in SCC cases from each region.
Type-specific prevalence of HPV in 1508 cases of adeno- and adenosquamous cervical carcinoma by region.