Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women

Abstract

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high-grade cervical lesions in Taiwan. The study included 1,086 paraffin-embedded, formaldehyde-fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR, direct sequencing and/or real-time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p 5 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91-2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.Human papillomavirus (HPV) is the primary etiologic agent of invasive cervical cancer (CC) and its precursors. 1 HPV DNA testing is a promising alternative or complementary test to improve the efficacy of cervical screening. 1,2 With the advent of the HPV vaccine, data on genotype-specific prevalence of HPV infection would be useful to predict the potential benefits of HPV vaccination. 3,4 Anogenital HPVs can be divided into high- (HPV16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and 82/MM4) and low-risk groups (HPV6,11, 40, 42, 43, 44, 54, 61, 70, 72, 81 and CP6108) according to the frequency of their presence in patients with cervical carcinoma. 5 In addition, HPV26, 53 and 66 are probably carcinogenic to humans. 5 The distribution of specific HPV genotypes in patients with CC varies greatly across populations. 6 The prevalence of HPV16, 18 and 45 is lower in high-grade squamous intraepithelial lesions (HSIL) than in invasive cancer (prevalence ratio for CC:HSIL 1.30, 95% CI: 1.26-1.34 for HPV16; and 1.76, 95% CI: 1.58-1.95 for HPV18). In contrast, the remaining highrisk types are significantly underrepresented in CC. These differences highlight the importance of HPV type in the risk of progression from HSIL to CC. 7,8 A meta-analysis including 7,094 cases of HSIL from all continents 8 has shown that the 8 most common HPV types in HSIL were broadly similar to those in invasive squamous cell carcinoma, the only exception being ...

Human papillomavirus in vaginal intraepithelial neoplasia

“…History of previous CIN (n ¼ 129) or cervical cancer (n ¼ 137) or concomitant CIN or cervical cancer (n ¼ 67), previous history of vaginal cancer (n ¼ 1), history of other gynecologic cancers with/without hysterectomy (n ¼ 7), hysterectomy for benign diseases (n ¼ 17) and isolated VAIN cases with intact uterus without concurrently documented CIN or cervical cancer (n ¼ 36) were recorded. The mean age of the VAIN cases was 59 years (median, 59 years; range, 19-93), which was significantly older than those with CIN2/3 (median, 47.5 years; range, 20-87) 19 (p < 0.0001). The mean ages of HPV-positive and HPV-negative VAIN cases were both 59 years.…”

“…The previously reported 1,086 cases of Grade 2 or 3 CIN (CIN2/3) were used for comparisons with VAIN cases in terms of age and genotype distribution. 19 The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital.…”

“…Finally, DNA was eluted in 100 lL of elution buffer, and 1 lL containing at least 25 ng of DNA was used for PCR amplification. 19 …”

“…19,20 Primer GP6þ was biotinylated at the 5 0 end. In CUT primer system, five primers were used according to Chouhy et al 21 The amplimer is 370 bp long.…”

“…The DNA sequences obtained from the patient samples were compared to the GenBank sequences using the BLAST Program at the National Center for Biotechnology Information. 19,20 Type-specific PCR reactions were performed to validate the presence of multiple types on the HPV blot. 20,22 In case of discordance between results, repeat HPV blot, type-specific PCR and direct sequencing were repeated to resolve the discrepancy.…”