Key words: human papillomavirus infection; cervical cancer, epidemiology; ChinaThere is strong epidemiologic evidence indicating that human papillomavirus (HPV) plays a central role in the etiology of cervical cancer. [1][2][3][4] The women positive for HPV DNA have a risk of developing cervical cancer 15-50 times higher than those without HPV DNA. 1,2,4,5 Although HPV infection is common among young women, only a small minority go on to develop cervical cancer. This situation was reviewed by a group of researchers, who concluded that viral persistence of oncogenic HPV appears to be crucial for the development of cervical cancer. 6 Indeed, HPV-16, -18, -31 and -33 have been officially declared to be oncogenic by the World Health Organization (WHO). 7 The International Biological Study on Cervical Cancer (IBSCC) study group revealed that on average 92.9% of the tumors contained HPV DNA, with a range of 75-100%. 8 Although this international survey included 10 of the 18 regions of the world and provided the most extensive global view of HPV in cervical cancer, there were no data from China, 1 of the largest populations in the world. Furthermore, there are few published data from a well-designed study using a quality-controlled method on the prevalence of either HPV infection or HPV genotypes in cervical cancers in China.We conducted a multicenter study of HPV infection in cervical cancer by selecting 5 geographic regions of China: Shanghai (Eastern China), Guangzhou (Southern China), Sichuan (Western China), Beijing (Northern China) and Hong Kong (Specific Administration Region). MATERIAL AND METHODS PatientsCervical cancer specimens were collected from each of the 5 regions in China, including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. Each of the 5 settings (Tumor Hospital, Shanghai Medical University in Shanghai, Tumor Hospital, Sun Yat-sen University of Medical Sciences in Guangzhou, Second Hospital, West China Medical University in Sichuan, Tumor Hospital, Chinese Academy of Medical Sciences in Beijing, and Prince of Wales Hospital, The Chinese University of Hong Kong in Hong Kong) was responsible for collecting 150 or more tumor specimens consecutively from the year 1997 to 1999. Patients from Hong Kong were prospectively recruited with informed consent, and all specimens were freshly frozen. Those specimens collected in other parts of China were paraffin-embedded and retrieved retrospectively from the pathology files in those reference centers. Ethical approvals were obtained from each of the ethical review boards of the respective institutes. Histology reviewAll histologic slides submitted were reviewed by 1 of the investigators (M.K.M.C.) to reestablish the histologic type and

Adolescents have high rates of human papillomavirus (HPV) infection, and persistent high-risk HPV infection can lead to the development of cervical cancer. The cyclin-dependent kinase inhibitor, p16 INK4a is overexpressed in cervical intraepithelial neoplasia (CIN), probably due to a persistent and integrated HPV infection. This study investigated p16 INK4a expression, grades of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies were immunohistochemically stained for p16 INK4a . The presence of wide-spectrum, low-risk, or highrisk HPV was determined by amplifying DNA extracted from the cervical biopsies. Early sexual activity with multiple partners places many female adolescents at high risk for the future development of cervical cancer. The prevalence of human papillomavirus (HPV) infection in adolescents ranges from 19 to 46%, but the cervical intraepithelial neoplasia (CIN) in adolescents are predominantly low-grade and in the great majority of cases they resolve spontaneously. Only 0.12-3% of adolescents known to be infected with high-risk HPV develop high-grade CIN, and cervical carcinoma is extremely rare. 1-5 Woodman et al 4 reported that adolescents infected with HPV 16, 18, and 31 had a higher risk of developing high-grade CIN than persons infected with other oncogenic HPV types. Moscicki et al 6 observed that persistently positive high-risk HPV testing precedes the development of high-grade CIN.High-risk HPV DNA can be detected in almost all high-grade CIN and cervical cancers. 7,8 From a screening study of 7932 women aged 21-30 years, Clavel et al 9 reported that 23% had high-risk HPV infections. For the majority of women, the infections are transient and last 8-10 months. 9-11 It was the repeated positive high-risk HPV test results, reflecting persistent infection that predicted a likelihood of having a high-grade CIN. 3,9 In susceptible adolescents, either repeated exposure or an inability to suppress immunologically an infection may promote the oncogenic potential of

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.