Characteristics of the study population
Clinical information of 250,000 women who underwent HPV and TCT test at Qilu Hospital of Shandong University from January 2012 to January 2019 was retrospectively collected and analyzed. Among them, 7001(2.80%) women were diagnosed as ASC-US by TCT test, including 3459 (49.41%) women with hr-HPV infection and 3542 (50.59%) women without hr-HPV infection. Finally, a total of 3,459 ASC-US women with hr-HPV infection were enrolled in this study finally.
A total of 1973 women chose the HPV typing test, identified the specific types of hr-HPV they were infected with, among whom 376 were 12 hr-HPV positive (from Cobas 4800 HPV test), 1,043 women had single HPV infection, and 554 women had multiple HPV infections. 1245 women were diagnosed with hr-HPV positive by HC2 test. The remaining hr-HPV positive 241 women who lost their results of HPV test, were classified as ANY group in this study. (We did not know the specific genotypes, nor did we know whether it is a single infection or multiple infections. We only knew that they were hr-HPV positive by their medical records during this study period.)
The average age of women was 39.86±9.94 years (range: 15–80 years). The median number of pregnancies was 3 (range: 0–14) and the median number of births was 1 (range: 0–8).This study divided the age into 5 age groups ≤30 (n = 654, 18.91%), 31–40 (n = 1258, 36.37%), 41–50 (n = 1011, 29.23%), 51–60 (n = 448, 12.95%), and ＞60 (n = 88, 2,54%).
Distribution of histological results among different genotypes in ASC-US women
The common hr-HPV genotype were shown in Table 1 and Figure 1, in women with ASC-US. In addition, the 31–40-year-old group (n = 1243, 35.94%) and 40–49-year-old group (n = 1087, 31.43%) account for 65.6% of the total group.
This study calculated the rate of HSIL+ detection in women with HPV16, 18, 33, 39, 51, 52, 53, 56, 58, and 66 single infection (Table 2). And, other hr-HPV genotypes (except HPV 16, 18, 33, 39, 51, 52, 53, 56, 58, and 66) were grouped into the group of “others” due to the small number of people included in women with the single hr-HPV infection. The HSIL+ detection rates were different in different hr-HPV genotypes, and the rates of HSIL+ ranged from 8.51% to 63.09% in ASC-US women with single hr-HPV infection. The HSIL+ detection rate of women with single HPV16 infection (63.09%) was the highest, followed by HPV33(57.50%), HPV51(36.11%), HPV58(36.11%), HPV52(28.28%), HPV18(26.37%), HPV66(19.35%), HPV39 (18.92%), HPV53(15.00%), and HPV56(8.51%). The HSIL+ detection rate in the “others” group was 30.09% (Table 2). Overall, a total of 1403 women had single HPV infection, of which 414(29.51%) were diagnosed as HSIL and 22(1.57%) women were diagnosed as cervical cancer by histological test, and the rate of HSIL+ in women with single HPV infection was 31.08%.
Among women with the multiple infections, the HSIL+ detection rates in women with double hr-HPV infections, triple hr-HPV infections, and quadruple or more hr-HPV infections were 39.77%, 41.49%, and 45.00%, respectively (Table 2).
For those the specific hr-HPV types could not be identified, the detection rate of HSIL+ in ASC-US women with 12 hr-HPV test positive result (detected by Cobas 4800 HPV) was 32.45%, and the detection rate of HSIL+ in ASC-US women with hr-HPV positive results was 30.35% (Table 2).
A total of 45 (1.30%) of the women in this study were diagnosed with cervical cancer, including 24 women with HPV16 infections (including 19 women with HPV16 single infection and 5 women with HPV16 multiple infections), 3 women with HPV18 single infection, 1 woman with HPV33 single infection, 1 woman with 12 hr- HPV infection (from Cobas 4800 HPV test), and 16 women with unidentified hr-HPV genotypes infections (11 women were HC2 positive, and 5 women belonged to ANY group).
Distribution of histological results among viral load groups in ASC-US women
1245 women tested positive for hr-HPV by HC2 test. 42.93% (n = 398) of women with ASC-US had normal histological results, 22.76% (n = 211) had LSIL, 33.23% (n = 308) had HSIL, and 1.08% (n = 308) had cancer. 34.30% (n = 318) of women were diagnosed with HSIL+. According to the viral load of hr-HPV, women were divided into 3 groups: low viral load group (1≤RLU/CO<10, n = 189), medium viral load group (10≤RLU/CO <100, n = 212), and high viral load group (RLU/CO ≥100, n = 526).
The pathological distribution of these three viral-load groups was shown in Table 3. The percentage of women with normal pathology in the low-viral-load group (65.61%) was highest, followed by intermediate-viral-load group (41.98%) and high-viral-load group (35.17%). However, detection rate of HSIL+ in low-viral-load group was lowest, followed by intermediate-viral-load group (34.91%) and high-viral-load group (40.68%), and there was is statistically significant between detection rate of HSIL+ and hr-HPV viral load (χ2 = 35.03, P＜0.0001).
Distribution of histological results among age groups in ASC-US women
Overall, 43.51% (n = 1505) of women with ASC-US had normal histological results, 20.84% (n = 721) had LSIL, 34.35% (n = 1188) had HSIL, and 1.30% (n = 45) had cervical cancer. The rate of HSIL+ of hr-HPV-positive/ASC-US women was 35.65% (Table3). Age-stratified prevalence of HSIL+ and cervical cancer in hr-HPV-positive/ASC-US women is shown in Figure 2.
The HSIL+ detection rate of ≤30-year-old age group (40.52%) was the highest; however, the detection rate of HSIL+ (21.65%) was the lowest in the 51–60-year-old group. The HSIL+ detection rates of other age groups were 39.67% for group of women aged 31–40 years, 34.22% for group of women aged 41–50 years, and 29.55% for group of women aged >60 years. The women in ≤30 (OR = 2.465; 95% CI: 1.875–3.241), 31–40 (OR = 2.379; 95% CI: 1.850–3.060), 41–50 (OR = 1.883; 95% CI: 1.452–2.441) year-old groups had significantly higher risk of HSIL+ compared with those in 51–60-year-old group (OR regarded as 1.00). There was no statistically significant increase in the rate detection of HSIL+ in the group of ＞60 years by 36.49% (29.55% vs 21.65%; OR = 1.517; 95%CI: 0.911–2.527), compared with the 51–60-year-old group (Table 4).
The cervical cancer detection rates were 0.61%, 0.95%, 1.38%, 2.68% and 3.41%, respectively, in group of women aged ≤30 years, 31–40 years, 41–50 years, 51–60 years and >60 years. When regarding the rate of cervical cancer of women in ≤30-year-old group who had the lowest rate of cervical cancer as the compared baseline (OR as 1.00), the women in ≤51–60 (OR = 4.472; 95% CI: 1.433–13.957) and >60 (OR = 5.735; 95% CI: 1.262–26.064) year-old groups were at increased risk for cervical cancer. There was no statistically significant increase in the rates detection of cervical cancer in the group of 31–40 years by 55.74% (0.95% vs 0.61%; OR = 1.565; 95%CI: 0.503–4.872) and the group of 41–50 years by 126.23% (1.38% vs 0.61%; OR = 2.282; 95%CI: 0.748–6.963), compared with the ≤30-year-old group (Table 4).