p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: a prospective study in China.

p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16(INK4A) as a marker for the risk of low-grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A) immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1 predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A) Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43; 95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A) positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly associated with grade of CIN and risk of progression to high-grade CIN in women with low-grade lesions.

Seroprevalence of human papillomavirus types 6, 11, 16 and 18 in Chinese women.

BACKGROUND: Human papillomavirus (HPV) seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women. METHODS: Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles. RESULTS: A total of 4,731 women (median age 35, age range 14-54) were included, of which 4,211 were sexually active women (median age 37) and 520 virgins (median age 18). Low risk HPV 6 was the most common serotype detected (7.3%), followed by HPV 16 (5.6%), HPV 11 (2.9%), and HPV 18 (1.9%). Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8%) than virgins (2.5%) (P = 0.005). Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR) = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P < 0.001). With increasing number of sexual partners, women were at higher risk of seropositivity of any type (OR = 2.6; 95% CI: 1.7-3.9 for > = 4 partners versus 1 partner, P < 0.001). Wives were at higher risk of seropositivity for HPV 16/18/6/11 when reporting having a husband who had an extramarital sexual relationship (OR = 2.0; 95% CI: 1.6-2.5, versus those whose husbands having no such relationship, P < 0.001). There was a strong association between HPV 16 seropositivity and presence of high-grade cervical lesions (OR = 6.5; 95% CI: 3.7-11.4, versus normal cervix, P < 0.001). CONCLUSIONS: HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.

The association between dietary intake and cervical intraepithelial neoplasia grade 2 or higher among women in a high-risk rural area of China.

OBJECTIVE: To evaluate the relationship between dietary intake and risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) while controlling for human papillomavirus (HPV) infection. METHODS: In 1999 and 2002, 11,031 women aged 35­50, were screened as part of two cross-sectional population-based cervical cancer screening studies in China. Dietary food intake information was collected by a 79-item Food Frequency Questionnaire (FFQ). 748 HPV-positive women (557 normal biopsy; 95 CIN2, 79 CIN3 and 17 cancer) with completed interviews and biopsy results were included in our data analysis. Specific dietary food groups were classified into dark-colored vegetables, light-colored vegetables, onion vegetables, legumes, nuts, eggs, and meat. Unconditional logistic regression was used to evaluate the association between dietary intake and the risk of developing CIN2+. RESULTS: Inverse associations between CIN2+ risk and onion vegetables, legumes, nuts, and meat were observed. Comparison of the lowest and highest tertiles for consumption of onion vegetables, legumes, nuts, and meat yielded adjusted odds ratios (ORs) of 0.589 [95% confidence intervals (CI), 0.387­0.897; P for trend = 0.011], 0.591 (95% CI, 0.392­0.892; P for trend = 0.012), 0.635 (95% CI, 0.426­0.946; P for trend = 0.019), 0.624 (95% CI, 0.406­0.958; P for trend = 0.044), respectively, for CIN2+ risk among 748 HPV-positive women. No associations were found between CIN2+ risk and dark-colored vegetables, light-colored vegetables or eggs. CONCLUSIONS: Dietary intake of onion vegetables, legumes, nuts, and meat is associated with reduced risk of CIN2+. These foods may provide a protective factor against CIN2+.