Preplanned Studies: Detection and Associated Factors for Cervical Precancerous Lesions Among HIV-Positive Women from High HIV-Burden Areas — China, 2015−2016

Cervical cancer is the fourth most common cancer among women worldwide (1). Due to immunosuppression caused by human immunodeficiency virus (HIV) infection and the prolonged life expectancy associated with antiretroviral treatment (ART), cervical cancer has been one of the most common malignancies among HIV-positive women (2), and the World Health Organization (WHO) has recommended providing HIV-positive women with cervical cancer prevention and screening programs (3). An estimated 158,600 women in China are infected with HIV, but there is a lack of evidence to support the development of strategies for cervical cancer prevention and control that target HIV-positive women in China (4). Using data from a prospective study, we found that the detection rate of cervical intraepithelial neoplasia (CIN) grades 2 or worse (CIN2+) among HIV-positive women was 4.1% at baseline, and the incidence of CIN2+ was 0.1% in our follow-up survey. High-risk human papillomavirus (hrHPV) positive and early (<18 years old) sexual debut was associated with CIN2+ detection. The results draw attention to the need for regular cervical cancer screening among HIV-positive women and provides evidence on which to develop a cervical cancer screening program in China.

The data was derived from a prospective study on the co-infection of human papillomavirus (HPV) among HIV-positive women. The HIV-positive women were offered screening with an HPV test, cytology, and biopsy at baseline in 2015. The follow-up survey followed the same procedure as the baseline survey, which was conducted 1.5 years later on average. HIV-positive women aged 18–49 years were recruited from randomly selected townships in 5 counties of 3 high HIV-burden provincial-level administrative divisions (PLADs) including Yunnan, Guangxi, and Xinjiang. Eligible participants were those with no debilitating illness who had no previous history of cervical neoplasia or uterectomy. All participants provided informed consent to participate in the study. Ethical approval was obtained from the Institutional Review Board of the National Center for Women and Children’s Health, China CDC (No. FY2015–014).

A questionnaire survey was used to collect sociodemographic, reproductive, and sexual behavioral information. The medical records were reviewed to extract data on ART and laboratory results. Trained gynecologists provided gynecological physical examinations and collected cytological specimens. The cytological specimens were sent to a designated laboratory for cytological examination and HPV DNA test with the Cobas 4800 HPV test [Roche Molecular Diagnostics (Shanghai) Co. Ltd., Shanghai, China] to produce results for HPV16 and HPV18, and a pooled result on the other 12 hrHPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68b). In the baseline survey, another cytological specimen was collected and processed for 14 hrHPV types (16, 18, and the other 12 types).

HIV-positive women with cytology results of atypical squamous cells of undetermined significance (ASCUS) or worse (≥ASCUS) or hrHPV positive received colposcopy. The participants with abnormal colposcopy findings underwent biopsies, and those diagnosed with CIN2+ were referred for proper management. HIV-positive women with negative hrHPV and negative cytology or with negative colposcopy were deemed negative.

The blood samples were collected and tested for syphilis and hepatitis B surface antigen (HBsAg). The results of the CD4 lymphocyte count tests and HIV viral load tests within six months of when the fieldwork was conducted were either obtained from clinical records or from laboratory tests at the sites.

The analysis is based on women diagnosed with CIN2+ and those who had negative results from cervical screening in both baseline and follow-up surveys. The data was analyzed using SPSS software (version 23.0, IBM Corp, Armonk, NY, USA). We presented categorized variables as frequencies and proportions and used Pearson’s chi-square test and Fisher’s exact test as appropriate. Factors with a p-value of <0.1 were entered into a binary logistic regression to build the final model. A p-value of <0.05 was considered statistically significant and calculated for adjusted odds ratios (AOR) and 95% confidence intervals (95%CI).

The recruitment, screening, and diagnosistic processes are shown in Figure 1. During the baseline survey, 695 HIV-positive women were recruited, and 617 (88.8%) women completed the screening procedure. Of these, 25 women [4.1% (95%CI: 2.5%–5.6%) of those screened] had CIN2+. In the follow-up survey, among the 670 women who followed up, 462 (69.0%) completed the screening procedure, of whom two cases of CIN2+ [0.4% (95%CI: 0%–1.0%)] were detected. One of the two women (CIN3) was diagnosed with HPV58 infection, ASCUS, and CIN1, and another woman (CIN2) was diagnosed with HPV33/68 infection and negative cytology and colposcopy at the baseline. No cervical cancer was detected. The data of 27 women with CIN2+ and 442 women with negative results in both baseline and follow-up surveys were analyzed.

Figure 1. 

Cervical cancer screening and diagnosistic processes of the baseline and follow-up surveys among HIV-positive women from HIV high-burden areas in China, 2015–2016. Abbreviation: LBC=liquid-based cytology; hrHPV=high-risk human papillomavirus; HIV=human immunodeficiency virus; CIN=cervical intraepithelial neoplasia.

We present the univariate and multivariate analysis of sociodemographic characteristics, biological indicators of HIV infection, and STI coinfection between CIN2+ and negative women in Table 1. The distributions of age at sexual debut, hrHPV infection, and syphilis differed significantly between those two groups. Compared with women without hrHPV infection, those with single or multiple hrHPV infection or women with HPV16/18 or other hrHPV infection were more likely to have CIN2+ (trend χ²=81.84, p<0.001, trend χ²=30.69, p<0.001, respectively) (Figure 2). After controlling for age, we found hrHPV infection and early (<18 years old) sexual debut were associated with the occurrence of CIN2+ (AOR=49.1, 95%CI: 11.14–216.1, p<0.001; AOR=3.4, 95%CI: 1.2–10.2, p=0.03).

Figure 2. 

The detection of CIN2+ associated with different hrHPV infection groups among HIV-positive women from HIV high-burden area in China, 2015–2016. (A) Chi-square and p-value for trend for multiple hrHPV, single hrHPV, and no hrHPV was trend χ²=81.84, p<0.001. (B) Chi-square and p-value for trend for HPV16/18, other hrHPV, and no hrHPVwas trend χ²=30.69, p<0.001. Abbreviations: hrHPV=high-risk human papillomavirus; HIV=human immunodeficiency virus; CIN2+=cervical Intraepithelial neoplasia grades 2 or worse; other hrHPV=HPV31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68b.