Medical experts talk about popular science | Discuss the confusion and misunderstandings about cervical cancer prevention and control

Cervical cancer is one of the three major malignant tumors of the female reproductive system. In 2020, there were nearly 600,000 new cases of cervical cancer and about 340,000 deaths worldwide. The incidence and mortality rate ranked fourth among female malignant tumors in the world. In 2019, there were 111,000 new cases of cervical cancer and 34,000 deaths in China. Such high incidence and mortality rates are frightening and worrying. People can't help but ask,

Can cervical cancer be prevented and treated?

In fact, cervical cancer is a malignant tumor caused by infection. It is also the only malignant tumor with a clear cause. The culprit is human papillomavirus (HPV) infection. HPV infection is found in 99.7% of cervical cancer tissues. Therefore, preventing HPV infection can prevent the occurrence of most cervical cancers. Cervical cancer vaccines can prevent HPV infection; standardized screening and timely treatment of precancerous lesions can block the evolution of precancerous lesions into cervical cancer; standardized surgery, radiotherapy, and chemotherapy and other comprehensive treatments, for early cervical cancer patients, "cure" is no longer a dream. For this reason, in November 2020, the World Health Organization (WHO) issued the "Global Strategy for Accelerating the Elimination of Cervical Cancer" and planned the phased goals of cervical cancer prevention and control from 2020 to 2030: 90% of women are fully vaccinated with HPV vaccines before the age of 15; 90% of patients with cervical cancer receive treatment and care; 70% of women have had highly accurate cervical cancer screening between the ages of 30 and 45. Therefore, cervical cancer is a malignant tumor that can be prevented and treated.

Despite this, there are many misunderstandings and confusions about HPV infection, vaccine use, precancerous lesions, and cervical cancer:

1. Fear of HPV

They believe that as long as the HPV test is positive, they are not far from cervical cancer, which leads to anxiety and pessimism.

In fact, HPV infection is a common phenomenon among women. According to statistics, the cervical HPV infection rate in the normal population ranges from 6.1% to 33.5%, with an average of about 15%-20%. For individuals, the lifetime risk of HPV infection is about 80%-90%. After HPV infection, about 90% of them are transient infections, that is, they are naturally cleared by the body's immune system, and the average clearance time is about 12 months. Only about 10% of patients cannot be naturally cleared by the body, which is called persistent HPV infection. Persistent infection is a necessary condition for cervical cancer. However, only about 1%-4% of persistent infections may eventually develop into cervical cancer. Therefore, simple HPV infection is just a state, and the chance of causing cervical cancer is relatively low, so there is no need to panic.

Figure 1 Natural course of HPV infection (* HSIL is a precancerous lesion, LSIL is not a precancerous lesion)

2. Which HPV infections are closely related to cervical cancer?

There are more than 100 types of HPV, more than 30 types of HPV are related to reproductive tract diseases, and 14 types are related to cervical cancer, called high-risk HPV. The infection rate of HPV16, 18, 45, 31, 33, 52, 58 and 35 in cervical squamous cell carcinoma is as high as 95%, of which HPV16 and 18 account for more than 70% of cervical cancer, especially HPV16, which is the most common in cervical cancer. Currently in my country, sexual infections of HPV31, 33, 52 and 58 are also receiving more and more attention.

3. After HPV infection, what conditions are required for cervical cancer to develop?

High-risk, persistent HPV infection is a basic and necessary condition for the occurrence of cervical cancer. Whether cervical cancer can occur after HPV infection depends on the interaction between HPV and the host's inherent immunity and adaptive immunity, which is similar to the relationship between "seeds" and "soil". Low immune status and inability to establish an effective immune response are important factors leading to persistent HPV infection and cervical cancer. In addition, smoking, drinking, lack of sleep, oral contraceptives, early and frequent sexual activity, multiple sexual partners, and multiple births are also auxiliary factors in the occurrence of cervical cancer.

Figure 2 Conditions and evolution of cervical cancer

4. What evolutionary processes are required from HPV infection to cervical cancer?

The process from HPV infection to cervical cancer is a multi-step, complex and long process. Precancerous lesions are the inevitable transitional stage from HPV infection to cervical cancer, namely: transient HPV infection---persistent HPV infection---virus integration into host cells---precancerous lesions---cervical cancer. It takes about 10-15 years, so there is enough time to screen, detect precancerous lesions, and treat them in time.

Figure 3 From precancerous lesions to cervical cancer

5.How to screen for precancerous lesions?

Screening and treatment of precancerous lesions are secondary prevention of cervical cancer and are key cancer prevention measures besides HPV vaccines. Screening methods include HPV and TCT testing (alone or combined), colposcopy and histopathological examination, also known as the three-step examination; screening generally starts about 3 years after the start of sexual life. Screening can be stopped for those aged >70 years who have had more than 3 satisfactory normal cytology tests in 10 years. However, if there is no history of the above screening, or if the screening is abnormal, it is recommended to continue screening; the doctor will determine the screening interval based on the screening results (ranging from 1 to 5 years); attention should be paid during screening: avoid the menstrual period, prohibit sexual intercourse within 24 hours before screening, prohibit vaginal douching and vaginal medication within 48 hours before screening, and if there is inflammation in the vagina, it must be cured before examination.

6. Misunderstanding of "cervical erosion"

Some people think that cervical erosion is a precancerous lesion. In fact, cervical erosion is only a manifestation of the appearance of the cervix and is not a clinical diagnosis. Both precancerous lesions and early cervical cancer can present as an erosive appearance, and the two are easy to confuse. But in fact, cervical erosion is divided into physiological and pathological. In some cases, the physiological columnar epithelium of the cervix will migrate outward, and the appearance looks "eroded". This is a physiological phenomenon and does not require treatment. Pathological erosion is seen when pathogens infect the cervix and cause cervicitis. Therefore, when the cervix appears erosive, TCT and HPV tests are required first to rule out cervical precancerous lesions and cervical cancer.

7. Confusion about HPV vaccine

HPV vaccine is the primary prevention of cervical cancer. Can all people get vaccinated? How to choose the type of vaccine and the appropriate population? Do I need to test for HPV before vaccination? If high-risk HPV infection has been found, is it still useful to get vaccinated? Can women who are menstruating, breastfeeding, or pregnant get vaccinated? After vaccination, will I not get cervical cancer and do not need screening? Can the vaccine treat cervical cancer and precancerous lesions, or genital warts?

(1) Vaccine types and vaccination targets (see Figure 4)

Figure 4 Vaccine types and vaccination targets

(2) Obtaining information on whether HPV is positive before vaccination can be used to evaluate the preventive effect of the vaccine, but the purpose of HPV testing is to screen for precancerous lesions and cervical cancer. It is not necessary to do HPV testing specifically for vaccination. Regardless of whether HPV is positive before vaccination, HPV infection can be prevented after vaccination. Therefore, if HPV infection has occurred before vaccination, the vaccine can still be administered;

(3) Vaccination during menstruation is not a contraindication. Currently, there are no clinical trials to support its safety during pregnancy and pregnancy preparation. Generally, pregnancy can occur 3-6 months after vaccination. HPV vaccination is not recommended for pregnant women. If pregnancy is planned in the near future, it is recommended to postpone vaccination until after breastfeeding. If pregnancy occurs unexpectedly after vaccination, the unfinished doses should be stopped and subsequent vaccinations should be completed after delivery. However, there is no need to start a new process. Only the remaining unvaccinated injections need to be vaccinated. Given that many drugs can be secreted through breast milk and there is a lack of safety research data on HPV vaccination during breastfeeding, HPV vaccination is not recommended during breastfeeding.

(4) The coverage of cervical cancer vaccines is limited. The 2-valent and 4-valent vaccines can only prevent 70% of cervical cancer, and the 9-valent vaccine can only prevent 90% of cervical cancer. Therefore, HPV vaccines cannot prevent viral infections and cervical cancer that are not covered by the vaccine. Therefore, even if you have received the HPV vaccine, you still need to undergo regular screening for cervical cancer and precancerous lesions. The vaccines currently used are preventive vaccines and cannot treat existing cervical cancer, precancerous lesions or genital warts, nor can they prevent and protect against diseases caused by HPV types covered by the vaccine that have already been infected before vaccination.

8. How to prevent and detect cervical cancer early?

One of the main symptoms of early cervical cancer is abnormal vaginal bleeding, the most common manifestation of which is contact bleeding (vaginal bleeding after touching the cervix during sexual intercourse or gynecological examination). Elderly people who have already gone through menopause will experience irregular vaginal bleeding after menopause. The second symptom is abnormal vaginal discharge or abnormal vaginal discharge, such as bloody vaginal discharge, a large amount of watery or rice-like vaginal discharge, or even a foul odor. Late-stage patients will experience pain or symptoms corresponding to the affected organs, but a considerable number of cervical cancer patients do not have any special symptoms in the early stages, and these are the groups that are easily missed. Therefore, for individuals, paying attention to sexual hygiene, avoiding/reducing high-risk factors for cervical cancer (see above), getting preventive HPV vaccines within the age range, regular screening, and seeking medical treatment in a timely manner when symptoms occur are the keys to cancer prevention.

Author | Cui Manhua

Professor, chief physician, doctor of medicine, doctoral supervisor, member of the Communist Party of China. Currently the director of the Obstetrics and Gynecology Diagnosis and Treatment Center of the Second Hospital of Jilin University, the director of the Obstetrics and Gynecology Quality Control Center of Jilin Province, and the director of the Obstetrics and Gynecology Clinical Medicine Research Center of Jilin Province. Chairman of the Obstetrics and Gynecology Branch of Jilin Medical Association, Standing Committee Member of the Obstetrics and Gynecology Branch of the Chinese Medical Association, Standing Committee Member of the Obstetrics and Gynecology Branch of the Chinese Medical Doctor Association, Vice Chairman of the Minimally Invasive Branch of the Chinese Maternal and Child Health Association, Vice Chairman of the Reproductive Tract Disease Diagnosis and Treatment Branch of the Chinese Eugenics Association, and review expert of the Chinese Medical Science and Technology Award and the National Natural Science Foundation. At the same time, he is the deputy editor-in-chief of the Chinese Maternal and Child Health Magazine and the Obstetrics and Gynecology Channel of the Medical Reference News, the executive editor of the Modern Obstetrics and Gynecology Progress Magazine, the Chinese Practical Gynecology and Obstetrics Magazine, and the editorial board member of the Chinese Obstetrics and Gynecology Magazine. He has been engaged in clinical, scientific research, and teaching work in obstetrics and gynecology for 39 years.

| Discipline Introduction

The Obstetrics and Gynecology Diagnosis and Treatment Center of the Second Hospital of Jilin University was founded in 1948 by Professor Yin Yuzhang, a famous obstetrician and gynecologist in my country. The center is currently a Level 4 Gynecological Endoscopic Surgery Training Base of the National Health Commission, a Gynecological Endocrinologist Training Base of the Chinese Medical Doctor Association, a Critical Maternal and Child Treatment Center of Jilin Province, a Perinatal Medicine Research Center of Jilin Province, a Eugenics and Genetics Research Center of Jilin Province, a Medical Quality Control Center of Obstetrics and Gynecology of Jilin Province, a Clinical Medicine Research Center of Obstetrics and Gynecology of Jilin Province, a Key Laboratory of Eugenics and Reproductive Medicine of Jilin Province, a Key Laboratory of Targeted Diagnosis and Treatment of Gynecological Tumors of Jilin Province, an Excellent Undergraduate Teaching Team of Higher Education Institutions in Jilin Province, a Key Medical Specialty of Changchun City in the "Twelfth Five-Year Plan", and the core of obstetrics and gynecology teaching, scientific research and medical treatment in Jilin Province. It has won the honorary titles of National May 1st Women's Model Post, Provincial Health System Women's Civilization Demonstration Post, Changchun City March 8th Red Flag Collective, Advanced Unit of Maternal and Child Health Work during the "Eleventh Five-Year Plan", and Advanced Unit of Safe Midwifery in Changchun City.

The center consists of 5 gynecological treatment areas, 3 obstetric treatment areas, outpatient clinics, prenatal diagnosis center, reproductive medicine center, and research room. There are 356 open beds, more than 290,000 outpatient visits per year, and 13,000 surgeries per year. The first test-tube baby in the province was born in the Obstetrics and Gynecology Diagnosis and Treatment Center. The center was the first in the province to carry out single-port laparoscopic surgery for gynecological diseases, laparoscopic surgery for gynecological malignant tumors, the application of sentinel lymph nodes in gynecological malignant tumor surgery, pelvic floor reconstruction surgery, hysteroscopic fertility preservation surgery, laparotomy radical surgery for gynecological malignant tumors, internal iliac artery balloon implantation and embolization for the treatment of pregnant women with postpartum hemorrhage, uterine preservation strategy of cervical lifting and folding suture in case of dangerous placenta previa, cytological P16 immunochemical staining technology for the detection of cervical lesions, microsperm extraction, and improved long ovulation promotion program.