- Characteristics of study population
A total of 34,587 women between 25 and 65 years old attended our hospital for cervical cancer co-screening, 4,198 of which (12.1%) had hrHPV infection and 1,839 (5.3%) had abnormal cytology results (Figure 1). Multiple infections were detected in 676 of the 4,198 (16.1%) infected women. The most common hrHPV genotype was HPV16 (1,373, 32.7%), followed by HPV58 (680, 16.2%), HPV52 (571, 13.6%), HP53 (504, 12.0%), HPV33 (360, 8.6%) and HPV18 (301, 7.2%).
- Cytology-negative and hrHPV-positive results
A total of 2,897 of the 4,198 (69.0%) hrHPV infected women with cytology-negative and hrHPV-positive results were enrolled in the present study. The mean age of these women was 39.60 ± 8.99 years old, with a median of 40. The prevalence of hrHPV among women with negative cytology and hrHPV positivity was a little different from that among the whole population of women receiving cervical cancer co-screening. The top six hrHPV genotypes were HPV16 (874, 30.1%), HPV58 (452, 15.6%), HPV52 (395, 13.6%), HPV53 (380, 13.1%), HPV18 (224, 7.7%) and HPV33 (208, 7.2%). With respect to each hrHPV genotype, the percentage of women with negative cytology was higher in those infected with HPV59, HPV53, HPV45, HPV18 and HPV51 (Table 1).
- hrHPV genotype and HSIL+ incidence
Colposcopy was performed in 2665 women with negative cytology and hrHPV positivity. Colposcopy-guided biopsy and random biopsy was performed in 1,742 (1742/2665, 65.4%) women. A total of 204 women (204/2665, 7.7%) had HSIL+, including 26 women with cervical carcinoma (14 women with early stage infiltration, 53.8%, 14/26), 173 women (173/2665, 6.5%) had low-grade intraepithelial neoplasia (LSIL), and 2,288 women (2288/2665, 85.8%) had negative histology results or normal colposcopic results. In the HSIL+ group, the prevalence of the hrHPV genotypes was HPV16 (119, 58.3%), HPV52 (28, 13.7%), HPV58 (26, 12.7%), HPV33 (22, 10.8%), HPV31 (15, 7.4%) and HPV18 (12, 5.9%). The percentage of women infected with multiple hrHPV genotypes was 19.1% (39/204) in the HSIL+ group. In the squamous cervical cancer group, the prevalence of HPV16 (75%, 18/24) was prominent. Among the 7 cases of adenocarcinoma in situ and adenocarcinoma, 5 cases were HPV18-positive and 2 cases were HPV16-positive, including one case HPV18 and HPV33 dual infection (Table 1).
- hrHPV genotypes and their risk for the detection of HSIL+
The rate of histological HSIL+ did not differ significantly by age group (25−34, 35−44, 45−54 and 55−65 years old. P = 0.14, 0.16, 0.83, and 0.79, respectively). Of the 801 women with negative cytology and HPV16 positivity, 119 (119/801, 14.9%) women were confirmed as HSIL+ by histological diagnosis. Besides HPV16, the rate of histologic HSIL+ in each genotype was above 10% for HPV33 (22/187, 11.8%) and HPV31 (15/142, 10.6%). The rate of histologic HSIL+ in each genotype was lower than 10% for HPV52 (28/362, 7.7%), HPV58 (26/414, 6.3%), HPV18 (12/206, 5.8%) and et al. The detection rate of histological HSIL+ in women infected with HPV16 or HPV33 was significantly higher than that in women infected with the other hrHPV genotypes (P = 0.00, P = 0.03, respectively) (Table 2). The difference between the rate of histological HSIL+ in women infected with HPV18 and those infected with the other hrHPV genotypes was not statistically significant (P = 0.30) (Table 2). Compared to women infected with HPV16, the detection rates of histological HSIL+ had no significantly difference in women infected with HPV33 or HPV31 (P = 0.29, P = 0.19, respectively). Although HPV58, HPV52, HPV53 and HPV18 were four of the top six most common genotypes in women with negative cytology and hrHPV positivity, the detection rates of histological HSIL+ in each of these four HPV genotypes were significantly lower than those in women infected with HPV16 (P = 0.00, P = 0.001, P = 0.00 and P = 0.00, respectively). The detection rate of histological HSIL+ in women infected with multiple genotypes was significantly higher than those with a single infection (P = 0.03).
Among all 2,665 women with hrHPV-positive and cytology-negative results, following adjustment for age, the odds ratio (OR) for histological HSIL+ was 3.75 (95% CI = 2.79−5.05) in women with HPV16 infection. In women infected with HPV33, the OR for histological HSIL+ was 1.69 (95% CI = 1.04−2.72). And in women infected with HPV31, the OR for histological HSIL+ was 1.46 (95% CI = 0.83−2.57). Infection with HPV genotypes 18, 52 or 58 did not increase the risk of HSIL+ (OR = 0.72, 1.03, 0.78, 95% CI = 0.39−1.32, 0.68−1.57, 0.51−1.20, respectively). The OR for histological HSIL+ in women with HPV16/18/33 infection was higher than that in women with HPV16/18 infection (3.85 vs. 3.26, 95% CI = 2.79−5.31, 2.41−4.40, respectively). The odds ratio (OR) for histological HSIL+ was 4.21 (95% CI = 2.99−5.93) in women infected with HPV16/18/31/33. The odds ratio (OR) for histological HSIL+ was 5.73 (95% CI = 3.30−9.97) in women infected with HPV16/18/31/33/52/58 (Table 3).
HPV16/18 were detected in 129 of 204 (63.2%) women with histological HSIL+; by contrast, the top six hrHPV genotypes (HPV16/18/31/33/52/58) were detected in 190 (190/204, 93.1%) women. The difference was statistically significant (P = 0.00); however, the colposcopy per HSIL+ detection ratio also increased from 7.7 to 10.2. The addition of the HPV31/33 genotype to that of HPV16/18 increased the percentage of HSIL+ detection from 63.2% to 77.5% (P = 0.002), and the colposcopy per HSIL+ detection ratio only increased slightly from 7.7 to 8.1 (Table 3).