Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.
Cancer Vaccines/therapeutic use* ; Cervical Intraepithelial Neoplasia/prevention & control* ; Female ; Humans ; Papillomavirus Infections/prevention & control* ; Papillomavirus Vaccines/therapeutic use* ; Precancerous Conditions/therapy* ; Uterine Cervical Neoplasms/prevention & control*

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

Human papillomavirus (HPV) infection is very common but with limited therapies available. Although the prophylactic vaccination will be promoted worldwide soon, it can only show its benefits decades later. For individuals who already have established infections and dysplasias, it has little efficacy. In contrast, the therapeutic vaccines bridge the temporal deficit by fighting against the established HPV infections and HPV-related diseases. HPV oncogenes may be delivered in viral and bacterial vectors, in peptides or protein, in nucleic acid form, or in cell-based vaccines. This review summarizes the clinical trials of HPV therapeutic vaccines under the way and the different preclinical research strategies that are under investigations.
Animals ; Cancer Vaccines ; therapeutic use ; Cervical Intraepithelial Neoplasia ; therapy ; virology ; Condylomata Acuminata ; therapy ; virology ; Female ; Humans ; Papillomavirus Infections ; prevention & control ; therapy ; Papillomavirus Vaccines ; therapeutic use ; Uterine Cervical Diseases ; therapy ; virology ; Uterine Cervical Neoplasms ; therapy ; virology

OBJECTIVETo explore the distribution the tyes- of human papillomavirus (HPV) in cervical biopsy tissue or exfoliated cell specimen of Chinese women and to estimate the perspective of HPV prophylactic vaccine in China.

METHODSA total of 18 studies using polymerase chain reaction to detect HPV types were included in this Meta-analysis. There were 1335, 394, 381 and 2584 cases included in invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal group respectively. The overall HPV prevalence was estimated by adjusting the variables using unconditional multiple logistic regression model. HPV type-specific HPV prevalence rates of 18 types including HPV6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73 and 82 were estimated, after stratified by cervical lesion of Chinese women.

RESULTSIn ICC, HSIL, LSIL and normal group, the overall HPV prevalence rates were 82.7%, 88.5%, 69.3% and 13.1% respectively, and the HPV16 type-specific prevalence were 61.9%, 46.7%, 21.0% and 3.1%. HIPV16 was the predominant type in all cervical lesion specimen followed by HPV18 and 58 in ICC group, then HPV58 and 52 in HSIL, LSIL and normal. The estimated HPV16/18-positive fractions were 69.6%, 59.1%, 32.3% and 4.4% respectively in ICC, HSIL and normal. Data from the Meta-analysis showed that the top five common HPV types in ICC women were HPV16, 18, 58, 52 and 31 which contributed for 82.9% of the ICC. Thus the HPV16, 18, 31, 33, 35, 45, 52 and 58 were accounted for 87.7% ICC in China mainland.

CONCLUSIONThe proportional impact of HPV16/18 vaccine on ICC was estimated as high as 69.6% in China. HPV58 seemed the priority HPV type and should be emphasized enough to be included in the development of new generation HPV vaccine. However, more uniform standardized multi center studies were necessary to get more exact figure about HPV distribution in China.

Cervical Intraepithelial Neoplasia ; epidemiology ; prevention & control ; virology ; Cervix Uteri ; virology ; China ; epidemiology ; Female ; Humans ; Logistic Models ; Papillomaviridae ; classification ; isolation & purification ; Papillomavirus Infections ; epidemiology ; Papillomavirus Vaccines ; administration & dosage ; Prevalence ; Uterine Cervical Neoplasms ; epidemiology ; virology

The expression of N-myc down-regulated gene 1 (NDRG1) has previously been reported to be involved in the proliferation, differentiation, invasion and metastasis of cancer cells, but its role in cervical cancer is still unclear. This study aimed to investigate the expression of NDRG1gene in human cervical cancer and its effect on aggressive tumor behaviors. The NDRG1 expression in cervical tissues and cells was detected by RT-PCR. Specific expression plasmid pEGFP-N1-NDRG1-GFP was used to enhance the expression of NDRG1 in human cervical cancer cell lines. The mRNA and protein level of NDRG1 was assessed by RT-PCR and Western blotting, respectively. Its effects on cell proliferation, migration, invasion, cell cycle and apoptosis were detected by MTT, transwell migration assay and flow cytometry (FCM), respectively. The results showed that the expression of NDRG1 in cervical cancer tissues and cells was significantly lower than in normal cervical tissues (P<0.001). After transfection with pEGFP-N1-NDRG1-GFP, the mRNA and protein expression of NDRG1 was up-regulated in Siha cells, which suppressed cell proliferation (P<0.001), induced cell cycle arrest (P<0.05), reduced invasion and migration of Siha cells (P<0.05), but caused no cell apoptosis. Moreover, vascular endothelial growth factor (VEGF), a tumor-induced angiogenesis factor, was markedly reduced and E-cadherin, a cell adhesion molecule, was increased in the cells transfected with pEGFP-N1-NDRG1-GFP. It was concluded that up-regulated NDRG1 may play a role in the suppression of malignant cell growth, invasion and metastasis of human cervical cancer.
Adult ; Aged ; Cell Cycle Proteins ; genetics ; metabolism ; Cell Line ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Middle Aged ; Neoplasm Invasiveness ; prevention & control ; Neoplasm Metastasis ; prevention & control ; RNA, Messenger ; genetics ; metabolism ; Transfection ; Up-Regulation ; Uterine Cervical Neoplasms ; metabolism ; pathology

OBJECTIVE: To assess the association between condom use and oral contraceptive consumption and the risk of cervical intraepithelial neoplasia (CIN). METHODS: A cross-sectional study was conducted in Perth clinics. A total of 348 women responded to the structured questionnaire. Information sought included demographic and lifestyle characteristics such as the use of condom for contraception, consumption of oral contraceptive, and duration of oral contraceptive usage. Crude and adjusted odds ratio (OR) and associated 95% confidence interval (CI) were calculated using unconditional logistic regression models and reported as estimates of the relative risk. RESULTS: The prevalence of CIN was found to be 15.8%. The duration of oral contraceptive consumption among women with abnormal Papanicolaou (Pap) smear result indicating CIN was significantly shorter than those without abnormal Pap smear result (mean+/-SD, 5.6+/-5.2 years vs. 8.2+/-7.6 years; p=0.002). Comparing to < or =3 years usage, prolonged consumption of oral contraceptive for > or =10 years reduced the risk of CIN (p=0.012). However, use of condom for contraception might not be associated with a reduced risk of CIN after accounting for the effects of confounding factors (adjusted OR, 0.52; 95% CI, 0.05 to 5.11; p=0.577). CONCLUSION: Use of oral contraceptives, but not condoms, for contraception appeared to be inversely associated with CIN. Prolonged use of oral contraceptive demonstrated its benefits of reducing the risk of CIN.
Adult ; Cervical Intraepithelial Neoplasia/epidemiology/*prevention & control ; Condoms/*utilization ; Contraception Behavior/*statistics & numerical data ; Contraceptives, Oral/*administration & dosage ; Cross-Sectional Studies ; Drug Administration Schedule ; Drug Utilization/statistics & numerical data ; Female ; Humans ; Middle Aged ; Prevalence ; Risk Assessment/methods ; Socioeconomic Factors ; Western Australia/epidemiology