Cervical cancer is a complex disease caused by both genetic susceptibility and environmental factors. Inherited genomic variance, high-risk human papilloma virus (HPV) infection/integration, genome methylation and somatic mutation could all constitute one machine learning model, laying the ground for molecular classification and the precision medicine of cervical cancer. Therefore, for cervical screening, next generation sequencing (NGS)-based HPV DNA and other molecular tests as well as dynamic machine learning models would accurately predict patients with potential to develop the cancer, thereby reducing the burden of repeated screening. Meantime, genome-editing tools targeting HPV would emerge as the next generation gene therapy for HPV-related cervical lesions. In this article, we review the substantial progress on molecular mechanism of cervical cancer development and suggest the future for precise prevention and early treatment of cervical cancer.
Early Detection of Cancer ; Female ; Humans ; Mass Screening ; Papillomaviridae ; Uterine Cervical Neoplasms ; diagnosis ; prevention & control ; therapy ; virology

OBJECTIVE: To estimate the significance of the Pap smear as a screening tool for cervical cancer. METHODS: A total of 79,840 Pap smear results performed at Pusan Paik Hospital over the 20 year period from 1979 to 1998 were collected and analyzed. RESULTS: The number of Pap smear cases increased markedly during this period, and the results as a whole were classified as consisting of 96.4% normal and benign cytology, 2.2% pre-cancerous cytology, and 1.4% cervical cancer. The relative frequency of cervical cancer decreased from 1.6% in 1979 to 0.7% in 1998. About 64% of the Pap smears were distributed within the age range of 30 to 49 years, and the rate of cervical cancer increased with age, age of marriage and experience of childbirth (p<0.01). The overall agreement of Pap smear results with histologic diagnosis by one histologic degree was 92.7%(1,128/1,217) with 73 overestimated cases and 16 underestimated cases of Pap smear compared to histologic diagnosis. CONCLUSION: This result implies that the Pap smear is an excellent screening tool for cervical cancer with respect to both its scale and validity. Periodic and active Pap smear testing would be helpful for the secondary prevention of cervical cancer.
Busan ; Diagnosis ; Marriage ; Mass Screening ; Parturition ; Secondary Prevention ; Uterine Cervical Neoplasms

OBJECTIVE: Although a great deal of knowledge accumulated with regard to the causes and epidemiologic features of cervical cancer, primary prevention has not been particularly effective to date. Most efforts with regards of control of cervical cancer have been directed toward secondary prevention with cytologic smears in a screening program. The purpose of this study was to know the cervical smear histories in the women with neoplasia of uterine cervix at present. MATERIALS AND METHOD: Between June, 1993 and October, 1996, seventy women with invasive cervical carcinoma and eighty-seven women with cervical intraepithelial neoplasia(CIN) were interviewed about cervical smear histories to assess the frequencies of past smear at the Soonchunhyang University Hospital. RESULTS: The results were follows: 1. The mean age of the women with invasive cervical cancer and CIN were 55+/-9 and 42+/-11, respectively. 2. Of the 70 cases of cervical cancer, 61%(43/70) has not been screened, compared with 43%(37/87) in cases of CIN. 3. The mean ages at first smear in the cases of previous smear were 42+/-6 of 27 cancers, 37+/-7 of 50 CINs. The gap between the age at the first smear and the age at diagnosis were about 6 years in cases of cervical cancers, about 5 years in cases of CIN. 4. The most common symptom in cervical cancers was vaginal bleeding or postcoital bleeding(57%). Although 13%(9/70) were discovered during screening without symptom in the women with cervical cancers, 58%(52/87) were diagnosed incidently during screening in CIN. 5. Pap smear numbers before diagnosis were strongly associated with age and stage. Among women diagnosed with invasive cancer under the age of 49, 75% had at least one cervical smear. But, all women with cervical cancer over age of 65 have not been screened. Unscreened rates of stage I, II, III, and IV were 34%, 78%, 85% and 83% respectively. 6. Among 38 cases who had undergone radiation therapy, 82%(31/38) had not been screen in contrast to 38%(12/32) in the women who had undergone radical surgery. 7. Among women with previous smears in the cervical cancer, 20%(14/70) have been screened within 1year. CONCLUSION: It is likely to diagnosis cervical cancer who had normal papanicolau smear in recent. So papanicolau smear is examined carefully and other adjunctive test is help to diagnosis cervical cancer exactly, for example cervicography, HPV testing.
Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Diagnosis* ; Female ; Humans ; Mass Screening ; Primary Prevention ; Secondary Prevention ; Uterine Cervical Neoplasms* ; Uterine Hemorrhage ; Vaginal Smears

Cervical cancer is the most common malignancy of the female genital tract. Its incidence is still increasing with lower average onset age. Mass screening should be above prevention and treatment, and three screening programs, including the optimal program, the general program, and the basic program, are currently adopted in China. Cervical intraepithelial neoplasia (CIN) , a precancerous lesion, can be confirmed by the combined use of cytology, colposcopy, and histology and then managed with standardized approach. Human papillomavirus (HPV) infection is an essential factor during the development of cervical cancer, and persistent infection of high-risk HPVs may lead to CIN and subsequently develop to cervical cancer. High-risk HPV detection can be used for screening, differentiation of the atypical squamous cells of undetermined significance/ low-grade squamous intraepithelial lesion (ASCUS/LSIL) triage, and follow-up after treatment. The modern strategy of HPV infection is "to treat the disease, CIN, means to treat the virus, HPV". The licensing of HPV vaccine is an important event in cancer prevention, and this vaccine can be used for the primary prevention. However, early diagnosis and early treatment are still the most basic strategies for cervical cancer prevention and treatment.
Cervical Intraepithelial Neoplasia ; diagnosis ; therapy ; virology ; Early Diagnosis ; Female ; Humans ; Papillomavirus Infections ; diagnosis ; prevention & control ; therapy ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms ; diagnosis ; prevention & control ; virology

Cervical Intraepithelial Neoplasia ; diagnosis ; epidemiology ; prevention & control ; virology ; China ; epidemiology ; Female ; Humans ; Mass Screening ; Nucleic Acid Hybridization ; methods ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; diagnosis ; prevention & control ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms ; diagnosis ; epidemiology ; prevention & control ; virology ; Vaginal Smears

OBJECTIVETo evaluate the performance of visual inspection with acetic acid (VIA) in preliminary screening of cervical cancer and its precancerous lesions among Chinese women by meta-analysis of diagnosis.

METHODSPubmed, Cochrane, Wanfang, CNKI and Weipu databases were employed to search for citations using the MeSH terms as "acetic acid", "cervical intraepithelial neoplasia", and "cervical cancer" both in Chinese and English. Additional relevant references cited in retrieval articles were also searched.40 pieces of research paper related with screening of cervical cancer and precancerous lesions of cervical cancer in Chinese women by VIA were collected. Bivariate random effects model was adopted using SAS 8.02.

RESULTSTwenty-two studies including 23 330 cases were finally selected in the analysis, among which 19 studies were reported in Chinese and the other 3 in English. These studies were reported from 2004 to 2010 and the age-range of subjects was between 15 and 81 years old. Stratified analysis of diagnosis threshold showed that the pooled diagnostic odds ratio (DOR) of VIA for CIN1+ (4.11, 95%CI: 3.20 - 5.04) was similar to that for CIN2+ (4.45, 95%CI: 3.73 - 5.15). Either CIN1+ or CIN2+, the DOR in younger women (≤ 40 year) (4.22, 95%CI: 3.29 - 5.16; 4.53, 95%CI: 3.46 - 5.47) was also similar to it in older women (> 40 year) (3.66, 95%CI: 2.27 - 5.37; 4.26, 95%CI: 3.32 - 5.26). There was no difference in the screening performance between county-level doctors (DOR = 4.62, 95%CI: 3.13 - 5.93) and municipal-level doctors (DOR = 4.48, 95%CI: 3.71 - 5.16).

CONCLUSIONThe screening performances of VIA were relatively consistent among different lesion grades and aging groups of Chinese women. After professional training, there was no difference in performance between county-level hospitals and municipal-level hospitals.

Acetic Acid ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cervical Intraepithelial Neoplasia ; diagnosis ; prevention & control ; Female ; Humans ; Mass Screening ; methods ; Middle Aged ; Uterine Cervical Neoplasms ; diagnosis ; prevention & control ; Young Adult

Self-sampling is a method by which the subject collects the own specimens for disease detection. It has the advantages of strong privacy, convenient and simple operation, free time and place, etc. It can improve the compliance of people in remote areas, affected by traditional concepts, limited by working hours and underdeveloped transportation and medical treatment to participate in disease detection and screening. With the development of "Internet+health care" and "Internet+nursing service", home-based self-sampling testing will become a developing situation for disease detection and screening. Human immunodeficiency virus and Human papillomavirus infection bring a heavy burden to individuals and society. In the absence of effective and widespread primary prevention, secondary prevention, namely "early detection, early diagnosis and early treatment" is an effective measure to control the adverse consequences. At present, there are many researches on HPV and HIV self-sampling test, whose test results are highly reliable and highly accepted in the population, and is of great significance for improving the coverage rate of cervical cancer screening and the diagnosis rate of HIV carriers.
Female ; Humans ; Papillomaviridae ; Early Detection of Cancer/methods* ; Uterine Cervical Neoplasms/prevention & control* ; Alphapapillomavirus ; Self Care/methods* ; Papillomavirus Infections/prevention & control* ; Specimen Handling/methods* ; Mass Screening/methods* ; HIV Infections/diagnosis* ; HIV ; Vaginal Smears/methods*

Cervical cancer ranks the second common cancer in women, affecting women severely in developing countries. It is a critical issue to develop simple, rapid, accurate, safe, acceptable, and inexpensive screening tests which can be used in cervical cancer prevention programs in developing countries. Due to the shortage of funding and qualified cytological professionals in most developing countries, WHO has been actively promoting visual inspection with acetic acid/iodine solution (VIA/VILI) as the alternative approach to screening cervical cancer. After the discovery of a link between human papillomavirus (HPV) and cervical cancer, the HPV prophylactic vaccine and CareHPV test have been successfully developed. The cervical cancer will be the first cancer eliminated by the combination of vaccination, screening, early diagnosis and treatment.
Acetic Acid ; DNA, Viral ; isolation & purification ; Developing Countries ; Early Detection of Cancer ; methods ; Female ; Humans ; Iodides ; Mass Screening ; methods ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; virology ; Uterine Cervical Neoplasms ; diagnosis ; prevention & control ; virology

INTRODUCTIONA retrospective observational study was performed to evaluate the effectiveness of CervicalScreen Singapore (CSS), a National Cervical Cancer Screening Programme.

METHODSNational trends on incidence, mortality of cervical cancer and carcinoma in situ of the cervix before and after the launch of CSS were examined. Linear regression was used to calculate the average annual percentage change in age-standardised incidence and mortality rates. We also examined the operational measures of CSS, such as the women who joined the CSS programme and the diagnostic accuracy of Pap smears. The study was confined to women who consented to join CSS at government-funded polyclinics.

RESULTSNationally, there was a greater decline in the age-standardised incidence and mortality rates in the period 2004-2008 as compared to the period 1987-2003. Under CSS, a total of 99,759 Pap smears were performed on 81,087 women in the period 2004-2008. However, the number of first screens decreased from 18,434 in 2004 to 11,624 in 2008. Among women aged 25-69 years who had their first Pap smear screening and who were recommended for routine rescreen in three years, 10% had a subsequent rescreen within three years. Overall, the CSS programme was able to detect 0.37 invasive cancers per 1,000 screens in women aged 25-69 years.

CONCLUSIONThe CSS programme has contributed to a decline in the mortality and incidence of cervical cancer in Singapore. However, the challenges of increasing the screening uptake among eligible women need to be addressed.

Adult ; Age Factors ; Aged ; Early Detection of Cancer ; methods ; Female ; Humans ; Incidence ; Mass Screening ; methods ; Middle Aged ; Papanicolaou Test ; Registries ; Retrospective Studies ; Singapore ; Uterine Cervical Neoplasms ; diagnosis ; epidemiology ; prevention & control ; Vaginal Smears

BACKGROUND: Human papillomavirus (HPV) prophylactic vaccines, bivalent types for HPV-16/18 with 70% prophylactic expectation, have been developed based on the genotypes found prevalent in the western countries, but little is known for those in Korea. Using a DNA chip test, we evaluated the clinical efficacy of HPV genotype based on cervical abnormalities. METHODS: As the initial diagnostic tests, HPV DNA chip tests and Papanicolaou smear (PAP) were used for 1,211 subjects. Cervical colposcopy directed biopsies were performed for 626 among the 1,211 subjects within one month. RESULTS: The most frequently found genotypes in all HPV-positive specimens (n=445) were HPV-16 (22.0%), 58 (13.9%), 52 (11.0%), 51 (9.0%), 56 (8.5%), and 18 (7.2%). HPV prevalence was significantly higher in specimens where PAP and biopsy results were closer to malignancy. The HPV genotype distribution of the histologically confirmed cervical high-grade squamous intraepithelial lesions (HSIL) or carcinoma cases showed HPV-16, 58, 52, 18, and 33, in descending order. The HPV DNA chip sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of cervical HSIL or carcinoma were 76.9%, 70.1%, 72.1%, and 75.8%, respectively, Of these, the sensitivity and NPV were higher than those of PAP. PPV and NPV of HPV-16 were 90.5% and 60.7%, respectively, being the highest among the genotypes. CONCLUSIONS: We confirmed that HPV-16 genotype was also very important for the diagnosis of HSIL and cervical carcinoma in Korea. However, contrary to the findings in the western countries, the prevalence of HPV-58 was higher than that of HPV-18. Moreover, as the other HPV genotype reports were rare in Korea, further studies are required with the HPV DNA chip test before the nationwide adoption of the vaccines.
Adolescent ; Adult ; Aged ; Colposcopy ; DNA, Viral/analysis/isolation & purification ; Female ; Genotype ; Humans ; Middle Aged ; *Oligonucleotide Array Sequence Analysis ; Papillomaviridae/classification/*genetics/isolation & purification ; Papillomavirus Infections/*diagnosis/epidemiology/virology ; Papillomavirus Vaccines ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/*diagnosis/prevention & control/virology ; Vaginal Smears/methods ; Young Adult