A multicountry evaluation of careHPV testing, visual inspection with acetic acid, and papanicolaou testing for the detection of cervical cancer.

Globally, cervical cancer is the third leading cancer and fourth cause of cancer-related mortality in women.1 There is a high disparity for cervical cancer between higher-income and lower-income regions, with more than 85% of cervical cancer occurring in low- and middle-income countries.1 This difference is primarily due to the difficulty in implementing Papanicolaou test–based screening programs because of their complexity, need for highly trained providers for reading the samples, need for close quality control, and mediocre sensitivity of the test even in optimal conditions.2 Based on the absolute etiologic link between carcinogenic human papillomavirus (HPV) and cervical cancer, 2 new approaches for the prevention of cervical cancer have emerged, these are as follows: (1) HPV vaccination for preventing incident HPV infection in younger women3,4 and (2) carcinogenic HPV detection for screening for cervical precancer and cancer.5–11 Both vaccine and screening have demonstrated high degrees of efficacy in prevention of HPV infection or detection at a treatable stage, with maximum effectiveness when guided by an understanding of the causal model and applied in an age-appropriate manner.12 Although prophylactic HPV vaccination may be the ultimate prevention strategy, these vaccines do not treat preexisting HPV infections and precancerous conditions.13–15 Therefore, there are millions of at-risk women who will not benefit from HPV vaccination, and robust screening and management programs developed for low- and middle-income countries are needed to reduce the burden of cervical cancer. Additionally, because the HPV vaccines do not protect against all the oncogenic genotypes of the virus, screening is still required even among vaccinated cohorts. Several new screening strategies have emerged as options for areas with limited resources. Visual inspection with acetic acid (VIA) is a method based on the use of 5% acetic acid (vinegar) that, when applied to the cervix, makes the dysplastic epithelium turn white (acetowhitening), becoming visible on evaluation by the unaided eye. The sensitivity of VIA is variable; 2 recent meta-analyses have reported sensitivity of 70% to 80% for cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) or more severe diagnoses.16,17 One large randomized clinical trial in India found a 35% reduction in cervical cancer-related mortality after a single screening by VIA,18 whereas a second trial did not find a statistically significant reduction8 in cervical cancer-related mortality compared with those randomized to the no-intervention arm of seeking standard services. Another approach that has recently become available is a lower-cost DNA test for detection of carcinogenic genotypes of HPV.19 Recent studies have shown that HPV testing used in a screen-and-treat approach was more effective than VIA in reducing the prevalence of CIN2+,20 and when used in a more traditional program (ie, colposcopy and excisional treatment of histologically confirmed CIN2+), it was more effective in reducing cervical cancer mortality than VIA and Papanicolaou test.8 In response to the need for more robust screening tools for low- and middle-income countries, a public-private collaboration led to the development of careHPV (QIAGEN, Gaithersburg, MD), a simplified, robust, and affordable HPV test that could be used in low-resource settings under a wider range of ambient conditions. The test can be run in any room because it does not need running water or air conditioning, and the process is simple and can be completed by people with limited laboratory training. Preliminary results for careHPV were promising and compared favorably to the US Food and Drug Administration–approved Hybrid Capture 2 (hc2; QIAGEN).21 Human papillomavirus DNA testing offers the possibility of using self-collected vaginal samples for primary screening. The advantages of self-collection are that it does not require pelvic evaluation; therefore, the sample collection process could be completed without the need for a speculum or even a health center facility because the sampling can be done at the community level. A recently pooled analysis of data from 5 studies in China found that HPV testing of self-collected specimens was at least as sensitive for CIN2+ and CIN grade 3 (CIN3+) as liquid-based cytology using clinician-collected specimens,22 and another review showed that population coverage can be increased by offering self-sampling.23 Further studies were needed to demonstrate whether careHPV truly had wide applicability under a variety of settings and how it compared with the 2 standards, VIA and Papanicolaou testing, in a more realistic setting. We therefore conducted a multisite study in routine public health settings in India, Nicaragua, and Uganda using existing staff and resources to assess the clinical performance of careHPV with both clinician-collected and self-collected specimens, VIA, and Papanicolaou testing for detection of cervical precancer and cancer.