- Baseline characteristics
In order to analyse the attribution proportion of HPV types to precancerous lesions, there were 3,134 eligible patients who underwent histopathological examination after HPV genotype-specific test within 180 days. As shown in Figure 2, China can be divided into two parts, south and north, along the Qinling Mountains-Huaihe River line. Although the PLA General Hospital attracted the patients all over the country, 95% of the patients enrolled in this study were from northern China due to the location. The mean age of the subjects was 42.06 ± 10.82 years old, where the youngest was 17 years old and the oldest was 79 years old. 3029 (96.65%) were positive for HPV and the 2747 (87.65%) were positive for HR-HPV. The top five HPV genotypes are HPV16, 58, 52, 51 and 56. As for the pathological results, 1732 (55.26%) women had HSIL, 1354 (43.21%) women had LSIL, 35 (1.11%) women had normal cervical cytology. The distributions of age, cervical pathology, HPV genotypes and single/multiple HPV infection among the 3,134 patients are presented in Table 1.
Table 1 Distribution of age, cervical pathology, HPV prevalence, and Single/multiple HPV infection in patients (n=3,134)
Fig. 2 Geographical distribution of the recruited patients (n=3,134) in China
- Age distribution of patients with different HPV-type infections
Age-stratified HPV distribution of the patients in the study is shown in Table 2 and Fig. 3. In the group of <20 age, there were only 3 eligible patients and one of them was infected by two HPV types, leading to 25%, 50% and 25% infection rate for HPV16, 39 and 58, respectively. For the patients at the age of 20-34, the top five HPV genotypes were HPV16 (26.91%), 58 (12.54%), 52 (10.70%), 51 (7.33%) and 56 (6.09%); at the age of 35-49, the top five genotypes were HPV16 (28.51%), 52 (12.76%), 58 (12.71%), 18 (5.77%) and 51 (5.57%); at the age of 50-64, the top five genotypes were HPV16 (25.92%), 58 (12.14%), 52 (12.14%), 56 (8.88%) and 51 (6.63%); at the age of 65-80, the top five genotypes were HPV16 (25.17%), 58 (12.58%), 52(9.27%), 56(9.27%), 31(7.28%). In the patients at the age of 20-34 and 50-64, the overall prevalence of the HPV genotypes was quite similar where the top five HPV genotypes were the same but with slightly different order. However, with the regard to the 35-49 age group, HPV 18 which was not among the top 5 HPV infection types while accounted for 5.77%; at the age group 65-80, HPV 31 which also was not among the top 5 HPV infection types while occupied for 7.28%. Moreover, the prevalence of HPV16 was the highest among all the age groups except for the group of <20 in which the sample size was too small.
Table 2 Age-stratified HPV distribution (15-year interval) in patients (n=3,134)
Fig.3 Age-stratified HPV distribution in patients (n=3,134, including multiple-genotype infection, HPV6, 11, 16, 18, 21, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 67, 68 and 82 (%))
- Age distribution of patients in different grades of cervical lesions
In this study, the prevalence of HSIL reached a peak in patients between 35 and 49 years of age, which was later than the peak for LSIL lesions. Age-stratified distribution of different cervical lesions in the study were presented by Table 3. The prevalence of LSIL demonstrated two peaks at 20–34 and 35-49, where there was no statistical significance between 20–34 and 35-49. The peak age of the onset of LSIL was at 20–34 years of age, which was around 7 years earlier than that of HSIL which had a peak at 35-49 years of age. The patients with normal cervix lesions also showed two peaks at 35-49 and 50-64 (there was no statistical significance between 35-49 and 50-64). To clearly show the results, a line chart of the age distribution is shown in Fig. 4.
Table 3 Age distribution of different grade of cervical lesions (n=3,134)
Fig. 4 Age distribution of different grade of cervical lesions
- Frequency of infection with a single or multiple HPV genotypes in cervical lesions
As shown in Table 4, in all of HPV infected patients, infection with one, two, three, four, five, six, and seven genotypes of HPV was detected in 1732 cases, 726 cases, 248 cases, 65 cases, 22 cases, 8 cases and 2 cases, respectively. The frequency of a single HPV genotype infection was 55.26%, while that of multiple genotypes was 34.18%. Infection with two different genotypes was the most common multiple HPV infections, where the maximum multiple infections were seven genotypes. Among HSIL patients, infection with single, 2, 3, 4, 5, 6, 7 genotypes accounted for 60.7%, 21.6%, 7.3%, 3.3%, 0.8%, 0.2% and 0.1%, respectively. As the number of HPV genotypes increased, the attributable proportion to HSIL decreased (shown in Table 3). There were no statistical differences in the frequencies of multiple HPV genotypes amongst different cervical lesions, suggesting that increased numbers of HPV genotypes did not increase the risk for HSIL. As illustrated by Fig. 5, the distribution of different genotypes to HSIL, LSIL, Normal has been presented.
Table 4 Frequency of multiple HPV types in women with different precancerous grades
Fig.5 Stratified- multiple HPV genotypes in different cervical pathological results HPV (-), (HPV)Single type, Two types, Three types, Four types, Five types, Six types (%)
- Distribution of HPV genotypes in women with different cervical lesions
Among the 3,134 patients underwent histopathological examination after HPV test within 180 days, there were 3, 099 precancerous cases and 35 normal cases. 3,029 (96.64%) cases were positive for HPV and 2,747 (87.65%) cases were positive for HR-HPV. According to Table 5, in the group of HSIL, HPV16 (56.46%) was the most frequent genotype, followed by HPV58 (18.41%), 52 (16.22%), 31 (8.23%) and 51 (7.68%). It is crucial to note that HPV16 was attributed more to HSIL than HPV52 and 58. Moreover, there was no significant difference between the distribution of HPV52 and 58. HPV16 (24.18%), 52 (22.01%), 58 (21.34%),56 (14.23%) and 51 (13.05%) were the most frequently detected types in LSIL, and there was no statistical difference for these former four types in the attribution to LSIL. The percentage of cases of with HPV 16 detected was 56.46% and was markedly higher in the HSIL group. As for the patients with normal cervix, HPV16 was also the dominated HPV genotype which accounted for 40.0%. HPV31 (25%), 6,11 (20%), 52 (15%), 58 (15%) and 66 (15%) were also the common types detected in normal cytology cases.
Table 5 Distribution of HPV infection with a single genotype and multiple genotypes in women (n=3,134)