A New Technology For Cervical Cancer Screening

ObjectiveWomen suffering from cervical cancer showed an increasing trend Worldwide. Cervical cancer has become a major threat to womens health and now risen to a social and public health problem. In2008, there were approximately529,800cases and275,000deaths worldwide due to cervical cancer. The number of deaths will rise to410,000cases in2030. However, more than90%of new cases are below the age of70years old and the average age of death of each of invasive cervical cancer advanced at least17years than the previous70years of age. The new cases and deaths, the incidence of which is getting younger and younger, is far underestimate the influence of cervical cancer in the world. Moreover,85%of new cases occur in developing countries where the survival rates were substantially lower owing to presentation at relatively advanced stages. This data is13%of all cases of cervical cancer.The incidence of cervical cancer is the result of the formation of multi-factor. A striking variation of incidence of cervical cancer was reported in different regions of the world. And high-risk HPV type infections are also different. The country take an organized, planned, high-quality of precancerous prevention screening countries for cervical cancer whose mortality was significantly lower than the world average level. Because early diagnosis and early treatment can effectively prevent cervical lesions (cervical intraepithelial lesions class Ⅱ and Ⅲ grade-CIN2/3) from developing to early invasive cervical cancer. However, only a handful of developing countries can do so now.The primary cause of cervical cancer is human papillomavirus (HPV)-high risk HPV infection. Treatment or vaccine to prevent HPV infection can overcome cervical cancer. Currently, HPV genotypes are more than200kinds. Therefore, it is impossible to cover all types for vaccine. HPV vaccine, which was bivalent or quadrivalent covering the most common type of HPV16/18, was used to prevent cervical cancer in developed countries. However, it is not yet implemented in China. Because the distribution of HPV types in difference regions was striking variation. The types of developed countries vaccine can not cover specific regions in China. Therefore, it requires a long plan to understand the prevalence of HPV and research the HPV vaccine.To prevent cervical cancer, Papanicolaou and Traut published their famous monograph on vaginal cytology as a screening method for cervical cancer in1943. Since then, the Papanicolaou (Pap) test has become the most commonly used method to screen for cervical cancer. The remarkable success achieved in preventing cervical cancer is largely attributable to cytological screening tests. With the introduction of organized cervical cytological screening programs, the incidence of cervical cancer has been dramatically reduced. However, high-quality cytology-based screening programs require experienced cytological doctors. The cytological diagnosis depends on subjective judgment of the degree of abnormal morphological changes. In China, it was reported that approximately75,000women develop cervical cancer and40,000women die from the disease each year. The main reasons were the large population, which was the highest in the world, and the lack of doctors who lack experience in rural areas. Individual cytology tests, however, are only moderately accurate and do not achieve concurrent high sensitivity and specificity for the detection of precancerous lesions and treatable cancers. Therefore, acceptable program efficacy is only achieved by repeating the tests at relatively frequent intervals. An ideal screening method would allow for the efficient and inexpensive screening of all women regardless of their social situation. Therefore, the aim of this study was to explore a new technology of cytological diagnosis for cervical cancer screening which is cheap and not dependent on the subjective judgment of doctor.Materials and Methods1ObjectsA total of1120female who visited clinics for cervical cancer screening were enrolled consecutively from August2011to July2012by the Department of Cytopathology, Maternal and Child Health Hospital of Henan Province. The participants whose median age was35years (ranging from15to80years) were included using the following selection criterion:sex life, without medical treatment or surgery, without total hysterectomy, non-pregnant, miscarriage.2Methods2.1Cytological DiagnosisEach ThinPrep slide, which was stained with Papanicolaou, was evaluated for cervical cytology in the department of cytopathology at Maternal and Child Health Hospital of Henan Province by three academic cytopathologists blinded to case-control status. Cytological classifications of disease grade were made in conformity with the Bethesda2001criteria. A diagnosis was assigned to each case as having negative for intraepithelial lesion or malignancy (NILM) or having an epithelial cell abnormality such as ASC-US、ASC-H、LSIL、HSIL、SCC、AGC. In our study, the current criterion standard remained the Papanicolaou-stained smear method, with ASC as the threshold of positive and histological results used to follow up.2.2Histopathological DiagnosisThe specimens of suspicious lesions was collected in colposcopy, and then fixed, dehydrated, made after the Baptist wax-embedded, sliced operation biopsy, hematoxylin-eosin staining (H-E). The specimens were evaluated by two academic pathologists blinded to case-control status. They are negative for histopathological diagnosis:normal squamous/columnar epithelial cells, cervical inflammation and genital warts. Positive histopathological diagnosis include:cervical intraepithelial neoplasia grade Ⅰ (CIN I), CIN Ⅱ, CIN Ⅲ, cervical carcinoma in situ (CIS) and invasive cervical cancer.2.3Hybrid Capture2High-Risk HPV DNA TestThe presence of HPV DNA was detected by the hybrid capture assay (Digene Corporation, MD). This approach uses the second-generation genomic hybridization capture technology to detect13high-risk HPV type and5types of HPV low-risk type. The analytical sensitivity of this assay is1pg HPV DNA, which was equal to approximately100,000HPV genome equivalents. The approach includes cloth boards, denaturation, hybridization, hybrid capture and detection. HPV DNA testing positive for the cutoff value was greater than1.0.2.4New Technology (automation-assisted) for Cervical Cancer Screening ProgramThe slides were fixed, stained in hematoxylin, stained in acid alcohol and stained in lithium carbonate, respectively. Then, the slides were detected by the machine. The new technology included patented smart capture technology station and data management station, and the intelligent image database technology was compatible with industry standard formats. At the capture station, conventionally prepared and stained slides were automatically mapped using video techniques and then scanned by a microscope with a CDD video camera linked to a computer. The new technology can rapidly scan and capture20field-of-view images for each slide. These images were stored in the computer and can be processed by one imaging system with binarization technology and Canny computational theory-of-edge detection to identify stained nucleus. The data management station can identify the proportion of the regional share of unit pixels to calculate the nuclear size and regional blue channel grayscale value to calculate the nuclear staining concentration. The data management station can automatically analyze the number of the nucleus, the nucleus size and the depth of the nuclear staining. Then, the station made a scatter diagram and histogram.3Statistical analysisAll statistical analyses were performed using the SPSS version17.0statistical package for Microsoft Windows. Pearson’s x2test was used to evaluate the significance of differences between designated groups. The coefficient of consistency (k) was used to evaluate the differences in sensitivity and specificity among the TCT and the new technology. All tests in this study were2-sided and P<0.05was considered statistically significant, a was0.05for the significant level.Results1Comparison of diagnosis between New Technology and TCTThe concordance between the New Technology and TCT was96.34%, with931cases positive and148cases negative with both tests (k=0.857). Compared to the diagnosis of TCT, the sensitivity of the new technology was99.04%(931/940), whereas the specificity was82.22%(148/180). Accordingly, it can be known that the Youden index was0.81. The positive predictive value (PPV) and the negative predictive value (NPV) of the new technology were96.68%(931/963) and94.27%(148/157), respectively.2Comparison diagnosis of New Technology with HPV DNA (HC2) and HistopathologyAmong the1120cases diagnosed by new technology,146cases were determined simultaneously with histological analysis and HC2HPV DNA test (Table Ⅱ). Positive of new technology diagnosis was recorded in124cases (84.93%) and negative in22cases (15.07%). In the124positive cases, the HPV DNA test was positive in109cases (87.90%) and negative in15cases (12.10%), whereas69cases were positive and55cases were negative for histopathology. Of the22cases with negative result of the new technology,7cases (31.82%) had positive diagnoses of HPV DNA (HC2). Compared to the histopathological diagnosis, the sensitivity and the specificity of the new technology were98.57%(69/70) and27.63%(21/76), respectively. The PPV and NPV were55.65%(69/124) and95.45%(21/22), respectively. Conclusions(1) The concordance rate of new technology consistent with liquid-based cytology screening for cervical cancer is96.34%.(2) The sensitivity and specificity of the new technology for cervical cancer screening are98.57%and27.63%, respectively.(3) The negative predictive value and positive predictive value of the new technology, which can take on the burden of cervical cancer screening, are95.45%and55.65%, respectively.