Summary Background Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess ...whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. Methods We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. Findings 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7–98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3–87·9), compared with cytology (sensitivity 87·9% 95% CI 84·7–90·7, specificity 94·7% 93·5–96·0) and VIA (54·6% 48·0–61·2, 89·9% 86·8–93·0). Sensitivity did not vary by study or age (<35 years, 35–49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1–91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7–99·9) and increased specificity to 93·5% (95% CI 91·9–94·6). Interpretation HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups—including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Funding Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.
Summary Breast and cervical cancer are major threats to the health of women globally, particularly in low-income and middle-income countries. Radical progress to close the global cancer divide for ...women requires not only evidence-based policy making, but also broad multisectoral collaboration that capitalises on recent progress in the associated domains of women’s health and innovative public health approaches to cancer care and control. Such multisectoral collaboration can serve to build health systems for cancer, and more broadly for primary care, surgery, and pathology. This Series paper explores the global health and public policy landscapes that intersect with women’s health and global cancer control, with new approaches to bringing policy to action. Cancer is a major global social and political priority, and women’s cancers are not only a tractable socioeconomic policy target in themselves, but also an important Trojan horse to drive improved cancer control and care.
Summary Background A new test ( care HPV; QIAGEN, Gaithersburg, MD, USA) has been developed to detect 14 high-risk types of carcinogenic human papillomavirus (HPV) in about 2·5 h, to screen women in ...developing regions for cervical intraepithelial neoplasia (CIN). We did a cross-sectional study to assess the clinical accuracy of care HPV as a rapid screening test in two county hospitals in rural China. Methods From May 10 to June 15, 2007, the care HPV test was done locally by use of self-obtained vaginal and provider-obtained cervical specimens from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi province, China. All women were assessed by visual inspection with acetic acid (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and colposcopy with directed biopsy and endocervical curettage as necessary. In 2388 women with complete data, 441 women with negative colposcopy, but unsatisfactory or abnormal cytology or who were positive on HC2 or the new care HPV test, were recalled for a second colposcopy, four-quadrant cervical biopsies, and endocervical curettage. An absence of independence between the tests was not adjusted for and the Bonferroni correction was used for multiple comparisons. Findings Complete data were available for 2388 (94·4%) women. 70 women had CIN2+ (moderate or severe CIN or cancer), of whom 23 had CIN3+. By use of CIN2+ as the reference standard and area-under-the-curve analysis with a two-sided alpha error level of 0·0083, the sensitivities and specificities of the care HPV test for a cut-off ratio cut-point of 0·5 relative light units, were 90·0% (95% CI 83·0–97·0) and 84·2% (82·7–85·7), respectively, on cervical specimens, and 81·4% (72·3–90·5) and 82·4% (80·8–83·9), respectively, on vaginal specimens (areas under the curve not significantly different, p=0·0596), compared with 41·4% (29·9–53·0) and 94·5% (93·6–95·4) for VIA (areas under the curve significantly different, p=0·0001 and p=0·0031, for cervical and vaginal-specimen comparisons for the care HPV test, respectively). The sensitivity and specificity of HC2 for cervical specimens were 97·1% (93·2–100) and 85·6% (84·2–87·1), respectively (areas under the curve not significantly different from the care HPV test on cervical specimens, p=0·0163). Interpretation The care HPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. Funding Bill & Melinda Gates Foundation.
Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to ...provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years 49·6–50·4, 48·2 years 47·3–49·2, 46·8 years 46·6–48·1, and 55·5 years 54·9–56·1, respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Marató de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.
Summary Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer ...incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.
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