It is now believed that there is a clear relationship between cervical cancer and human papillomavirus (HPV) infection in women. There is a long, reversible precancerous phase of cervical cancer, while early cervical lesions are treated much better than cervical cancer. The five-year survival rate has been reported to be 67% for invasive cervical cancer, 90% for early cervical cancer, and almost 100% for cervical cancer in situ. Therefore, screening and prevention of cervical cancer is of great importance.
Since the birth of Pap smear in 1941, the method has been introduced as a means of cervical cancer screening and used as a routine screening program in countries around the world, and has reduced the incidence of cervical invasive cancer in the screened population by 70% to 90% in one stroke, while the incidence level in the unscreened population has not changed much. It is still used in some places because of its simplicity, painlessness to the patient, and low cost, making it ideal for screening large populations.
Despite the overall success of Pap smears, there are still problems with their use.
On the one hand, the basic facilities required to set up a satisfactory cytology program are considerable, especially for cytology technicians who require long and rigorous training and several years of practical experience before they can identify the results of Pap smears more consistently and accurately.
On the other hand, the accuracy of Pap smears is affected by many factors, such as smear taking method, smear production, staining technique, and reading level, which inevitably lead to false negatives, with a false negative rate of about 15% to 40%.
Nowadays, the false-negative rate has decreased with the introduction of thin-layer liquid-based cytology to Pap smears, and in 1998, a large-scale survey was conducted at a site with a high incidence of cervical cancer in Shanxi, China, which confirmed its sensitivity and specificity of 87% and 94% in identifying highly lesive lesions.
In addition, automatic screening devices have been developed and brought to market to address the problem of false negatives in Pap smears, and representative ones are the PAPNET system and the AutoPap system. the PAPNET system is a neural network interaction device that is mainly used for cytological re-screening. For in situ and invasive cancers, the detection rate and accuracy of PAPNET are significantly higher than those of conventional methods. And a comparative study of AutoPap and conventional screening methods showed that AutoPap was superior to conventional methods in confirming atypical squamous cells and low-grade squamous intraepithelial lesions. In addition AutoPap improves the specificity of the diagnosis by reducing false positive cases.
HPV testing
Improves cervical cancer screening
Current epidemiological and biological data have demonstrated that HPV infection is the most important cause of cervical cancer and its precancerous lesions. Therefore, many scholars have proposed testing for HPV infection as a screening tool for cervical cancer.
HPV infection can be generally classified into high-risk, low-risk, transient, delayed and persistent types, with high-risk persistent infection being the most important. Therefore, the clinical applications of HPV testing include screening, management of abnormal cytology and follow-up after treatment of cervical lesions. Although there is some controversy regarding the use of HPV testing as a screening component, a European screening data including 23,890 patients showed that HPV testing significantly improved screening outcomes.
HPV is the only fully identifiable oncogenic virus in human carcinogenesis. Today’s research even confirms that prevention of HPV infection can prevent cervical cancer, and the absence of HPV infection can prevent cervical cancer. hC2 is the best method for HPV detection, with a sensitivity of 88% to 100% and a negative predictive value of 99%. hC2 negativity confirms the absence of HPV infection. The method can also report the amount of virus to follow the viral wax and wane.
It is understood that HPV infection is common, but only persistent HPV infection results in precancerous lesions (CIN) or cervical cancer. Generally HPV persistent infection can occur in an average of 8 to 24 months for CINI stage, CIN stage II and CIN stage III, and then an average of 8 to 12 years for invasive cancer.
Follow-up after treatment of cervical precancerous lesions is very important because the recurrence rate of patients with precancerous lesions after treatment is five times higher than that of the normal population. After treatment, patients with precancerous lesions should have their first review at 4-6 months, including visual observation, cytology, HPV DNA testing, or colposcopy if appropriate.
HPV vaccine: the most promising tool for the future
There is still no definitive solution to HPV, so more people are pinning their hopes on the HPV vaccine.
There are 3 ways to develop an HPV vaccine. The first is a prophylactic vaccine to prevent HPV infection, which is mainly used in young women before they become infected with HPV and is not effective in women who are already infected with HPV or have existing cervical precancer and cervical cancer. The second is a therapeutic vaccine used to treat patients who are already infected with HPV or have existing cervical lesions. The third type is a vaccine that has both preventive and curative effects.
In the past decade, HPV vaccine research and development has made great progress, with many products having completed Phase 1 and 2 clinical trial studies. on June 8, 2006, the U.S. Food and Drug Administration (FDA) officially approved the Gardasil cervical cancer preventive vaccine for clinical use in women aged 9 to 26. This is the world’s first oncology vaccine.
After efforts, China is basically on par with international standards in the development of HPV vaccines. In the development of HPV16 preventive vaccine, China has completed the construction of HPV16 L1 and L1/L2 recombinant baculovirus vaccine strains and expressed them in insect cells; observed the formation of virus-like particles under electron microscope; and successfully constructed recombinant replicative and non-replicative poxvirus vaccine strains with both L1/L2 expression.
In the development of HPV16 therapeutic vaccines, recombinant replicative and non-replicative poxvirus vaccine strains expressing HPV16 type E6/E7 proteins have been constructed in China. These vaccine strains have been tested to have good immunogenicity, induce specific CTL responses, and protect C57 mice against TC-1 tumor cell attack. Compared to controls, vaccination with this vaccine resulted in delayed subcutaneous tumorigenesis and significantly longer survival in the tumor-bearing mice.
When researchers immunized mice after tumor surgery with this HPV therapeutic vaccine, they found that this vaccine was effective in preventing tumor recurrence in mice. It is especially valuable in killing residual or metastasized tumor cells after tumor surgery, as well as in preventing tumor metastasis. These research results have laid the foundation for the development of genetically engineered HPV vaccine in China.