Wang Hongbo, Professor of Obstetrics and Gynecology, Wuhan Union Medical College Hospital
At present, there is a clear relationship between cervical cancer in women and human papilloma virus (HPV) infection. Cervical cancer has a long and reversible period of precancerous lesions. At the same time, the treatment effect of early cervical lesions is much better than that of cervical cancer. According to reports, the five-year survival rate for invasive cervical cancer is 67%, early cervical cancer is 90%, and cervical carcinoma in situ is almost 100%. Therefore, screening and prevention of cervical cancer is of great significance.
New changes in ancient methods
Fewer false negatives in Pap smears
Since the birth of the Pap smear in 1941, countries around the world have introduced the method into the clinic as a means of cervical cancer screening and used it as a routine screening program, reducing the incidence of cervical invasive cancer in screening populations by 70%. ～ 90%, and the incidence of unscreened populations has not changed much. Because of its simple method, no pain for patients, and low cost, it is very suitable for a large-scale population survey, and it is still used in some places.
Despite the overall success of Pap smears, their use remains problematic. On the one hand, the basic facilities required to establish a satisfactory cytology inspection project are considerable, especially cytology technicians, who need long-term and rigorous training and years of practical experience before they can more reliably and accurately identify Pakistan. Results of a smear. On the other hand, the accuracy of Pap smears is affected by many factors, such as the method of smear selection, smear production, staining skills, and reading level, etc., which will inevitably lead to the occurrence of false negatives. The false negative rate is approximately 15% to 40%.
Today, with the introduction of thin-layer liquid-based cytology, Pap smear tests have reduced the rate of false negatives. In 1998, a large-scale census was performed using thin-layer liquid-based cytology at the high-risk detection site of cervical cancer in Shanxi, China, which confirmed that the sensitivity and specificity of identifying high-grade lesions were 87% and 94%.
In addition, in response to the problem of false negatives in Pap smears, automatic screening devices have been developed and introduced to the market. The representative ones are the PAPNET system and the AutoPap system. PAPNET system is a neural network interaction device, which is mainly used for cytology rescreening. For carcinoma in situ and invasive carcinoma, the detection rate and accuracy of PAPNET are significantly higher than conventional methods. A comparative study of AutoPap and conventional screening methods shows that AutoPap is superior to conventional methods in the diagnosis of atypical squamous cells and low-grade squamous intraepithelial lesions. In addition, AutoPap can improve the specificity of diagnosis by reducing false positive cases.
May improve cervical cancer screening
Current epidemiological and biological data have proven that HPV infection is the most important cause of cervical cancer and its precancerous lesions. Therefore, many scholars have proposed detecting HPV infection as a screening method for cervical cancer.
Generally, HPV infection can be divided into high-risk, low-risk, transient, delayed and persistent types. High-risk persistent infection is the most important. Therefore, the clinical application of HPV detection includes screening, treatment of abnormal cytology, and follow-up after treatment of cervical lesions. Although there are some controversies regarding the use of HPV testing as a screening content, a European screening data of 23,890 patients showed that HPV testing can significantly improve the screening effect.
HPV is the only fully identifiable oncogenic virus in human cancer. Today's research can even confirm that prevention of HPV infection can prevent cervical cancer, and without HPV infection, cervical cancer can be avoided. There are many methods for detecting HPV. Currently, hybrid capture technology (hC2) is the best. Its detection sensitivity is 88% ~ 100%, and the negative predictive value is as high as 99%. If hC2 is negative, it can be confirmed that there is no HPV infection. The method can also report the amount of virus to follow the growth and decline of the virus.
It is understood that HPV infections are common, but precancerous lesions (CIN) or cervical cancer can occur only with persistent HPV infections. In general, HPV continuous infection can occur in CINI stage, CINⅡ stage, and CINⅢ stage in an average of 8 to 24 months, and invasive cancer can occur in an average of 8 to 12 years.
The follow-up of cervical precancerous lesions is very important, because the recurrence rate of patients with precancerous lesions is 5 times that of the normal population. After receiving treatment for patients with precancerous lesions, the first review will be performed in 4 to 6 months, including visual observation, cytology, HPV DNA testing, or colposcopy as appropriate.
The most promising means of the future
At present, humans still lack the exact method to deal with HPV, so more people will pin their hopes on HPV vaccine.
There are three ways to develop HPV vaccines. The first is a preventive vaccine to prevent HPV infection. It is mainly used before young women are infected with HPV. It is not effective for women who have been infected with HPV or have cervical precancerous lesions and cervical cancer. The second is a therapeutic vaccine, which is used to treat patients who have been infected with HPV or have cervical lesions. The third is a vaccine that has both preventive and therapeutic effects. In the past ten years, the development of HPV vaccine has made great progress, and many products have completed Phase 1 and 2 clinical trials. On June 8, 2006, the US Food and Drug Administration (FDA) officially approved the marketing of the Gardasil cervical cancer preventive vaccine. The clinical use of the vaccine is for women aged 9 to 26 years. This is the world's first tumor vaccine.
After efforts, China has basically been in line with international standards in the development of HPV vaccines. In the development of HPV16 preventive vaccines, China has completed the construction of HPV16 L1 and L1 / L2 recombinant baculovirus vaccine strains and expressed them in insect cells; the formation of virus-like particles was observed under an electron microscope; success Recombinant replication and non-replication vaccinia virus vaccine strains expressing L1 / L2 were constructed.
In the development of HPV16 therapeutic vaccine, China has constructed recombinant replication and non-replication vaccinia virus vaccine strains expressing HPV16 E6 / E7 protein. After testing, these vaccine strains have good immunogenicity, can induce specific CTL responses, and can protect C57 mice from attack by TC-1 tumor cells. Compared with the control group, the subcutaneous tumor formation time of mice was delayed and the survival time of tumor-bearing mice was significantly prolonged. When the researchers used the HPV therapeutic vaccine to immunotherapy mice after tumor surgery, they found that the vaccine could effectively prevent tumor recurrence in mice. In particular, it has certain application value on tumor cells remaining or metastasized after killing tumors, and on preventing tumor metastasis. These research results have laid the foundation for the development of genetically engineered HPV vaccine in China. (Health News)