The key to prevention and early detection of cervical cancer lies in effective screening and proper management of precancerous lesions.
I. Cervical cytology screening
1. Screening methods and diagnostic reports of cervical cytology: Pap smear has been the main method of cervical cancer screening for more than 70 years. In recent years, cervical thin-layer liquid-based cytology (TCT) has been introduced into cervical cancer screening, which can significantly improve the satisfaction of specimens and the detection rate of abnormal cervical cells, and gradually replace Pap smear as the main method of cervical cytology screening. At present, the diagnostic report of cervical cancer cytology screening adopts the International Society of Gynecologic Pathology TBS2001 grading and no longer follows the Pap smear grading. The diagnostic report first classifies cervical cytology specimens as satisfactory or unsatisfactory, and the reasons for unsatisfactory specimens are indicated and a repeat test is recommended. Then the presence of pathogens such as trichomonas, mycobacteria, mycoplasma, actinomycetes and human papillomavirus (HPV) infection is reported.
Finally, the diagnosis is reported in the following categories: negative (i.e., no intraepithelial neoplasia or cancer cells, including normal range and benign reactive changes), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells without exception of high grade lesions (ASC-H), low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), squamous cell carcinoma, atypical typical glandular cell (AGC), adenocarcinoma.
2. Screening initiation: The latest ACOG circular states that the age of initiation of cervical cancer cytology screening should not be earlier than 21 years. The reason for this change is that although HPV infection is common among adolescents and young women, most of them will be cleared by the body within 1-2 years, and the incidence of invasive cervical cancer in this population is very low, so cervical cancer screening is not recommended in women younger than 21 years old to avoid unnecessary worry and anxiety, over-surveillance and invasive screening.
3. Screening interval: The latest ACOG circular suggests that for women without CIN and cervical cancer risk factors, screening need not be too frequent. For women aged 21-29 years, screening should be done once every 2 years. For women over 30 years of age, screening may be extended to once every 3 years if 3 consecutive negative cervical cytology screens are performed. However, shorter screening intervals are needed if there are high-risk factors associated with CIN or cervical cancer.
These risk factors include human immunodeficiency virus (HIV) infection, immunosuppressed status (e.g., after kidney transplantation), maternal estrogen use during fetal life, and treatment for CIN 2 or 3 or cervical cancer. Specifically, HIV-infected women should be screened for cervical cancer twice within the first year of diagnosis and once a year thereafter. For women who have been treated for CIN2, 3 or cervical cancer, they should be screened once a year for at least 20 years after treatment.
4. Screening termination time: The latest ACOG circular suggests that for women over 65 or 70 years old, screening can be stopped if the results of 3 consecutive screenings are normal and no abnormalities have been detected in the last 10 years. However, there is no upper age limit for women who have CIN or high risk factors for cervical cancer and whose cervix is still preserved; for women who have had a total hysterectomy for other benign gynecologic conditions rather than cervical problems (such as fibroids or benign ovarian tumors) without previous high-grade cervical lesions and who have pathologically confirmed no cervical lesions, screening can be stopped after surgery; however, if the patient has had a hysterectomy for CIN 2, 3 or even more severe lesions However, if the patient has had her uterus removed for CIN 2, 3 or even more severe lesions, screening should still be performed after surgery. The screening interval can be extended, but there is no termination time.
II. About HPV testing and HPV vaccine
1. HPV testing: There are more than 100 subtypes of HPV, and only high-risk HPV types cause cervical lesions and cervical cancer, so HPV testing should target high-risk types. Currently, it is believed that hybridization capture II (HC II) HPV-DNA testing is the most accurate HPV testing method.
HPV testing is generally considered to have the following uses.
(1) Triage: For women 21 years of age and older, when the cervical cytology diagnosis is ASC-US, colposcopy is recommended if HPV is positive, and cervical cytology is repeated at 3-6 months of shade. Similar triage can be done for LSIL in older women over 65 years of age by testing for HPV.
(2) Follow-up: For women with a cytologic diagnosis of ASC-US, ASC-H, LSIL, or AGC and a negative colposcopic biopsy or CIN1 only, follow-up with HPV testing is available. HPV testing may also be used for follow-up in patients with treated CIN 2 or 3. Similar to cervical cytology screening, HPV testing is not recommended in young women under 21 years of age, and if the test is inadvertently performed, the results are not used as a basis for follow-up management.
2. HPV vaccine: HPV vaccines are divided into therapeutic and prophylactic vaccines, and those currently on the market are all prophylactic vaccines. The quadruple HPV vaccine Gardaci is the first HPV vaccine approved by the U.S. Food and Drug Administration to prevent CIN caused by HPV subtypes 16 and 18, and is currently considered to have an effective immunization period of at least 5 years for women aged 9-26. However, the best time to receive the vaccine is before the woman has sexual contact, and its immune effect decreases greatly after having sex, so HPV vaccination is recommended routinely for girls aged 1-12 years. It is important to emphasize that even after vaccination, women should still be screened for cervical cancer.
III. Colposcopy and biopsy, cervical canal scraping
Both ACOG and ASCCP consider cervical cytology as the initial screening tool for cervical cancer and colposcopy should be performed only in women with indications. With regard to colposcopy, the ASCCP believes that several points need to be emphasized: first, it is important to clarify whether colposcopy is satisfactory (i.e., whether the migratory zone is fully exposed) and to describe abnormal changes, second, it is important to perform multi-point biopsy of suspicious lesions under colposcopic guidance, and finally, it is important to decide whether to perform cervical canal scraping (ECC) based on whether colposcopy is satisfactory and age.
1. Non-pregnant women aged 21 years and older (called general population): colposcopy and biopsy are recommended for women with cervical cytology reported as ASC-H, LSIL, HSIL, regardless of HPV positivity. For women reporting ASC-US, there are 3 optional measures.
(1) Triage by HPV testing, colposcopy in positive cases, and repeat cytology in 3-6 months in negative cases.
(2) Direct colposcopy.
(3) repeat cytology at 6 months after observation and treatment of underlying inflammation.
Colposcopy is recommended in all women with AGC reported on cervical cytology, with ECC or diagnostic curettage as appropriate. If the patient is <35 years old and has no endometrial high-risk factors, ECC is sufficient; if the patient is ≥35 years old or has high-risk factors for endometrial cancer, abnormal vaginal bleeding, or atypical endometrial glandular cells are found, diagnostic curettage should be performed.
2. Pregnant women: It is generally considered safe to perform cervical cytology during pregnancy, but colposcopy and cervical biopsy need to be performed with caution, and ECC is contraindicated during pregnancy. For ASC-US in pregnancy, colposcopy can be postponed until 6 weeks after delivery; for LSIL in pregnancy, colposcopy is feasible and can also be postponed until 6 weeks after delivery. Colposcopy is recommended for HSIL or more severe lesions in pregnancy and for AGC. If colposcopy suspects CIN 2 or 3 or cervical cancer, a cervical biopsy is indicated.
3. Postmenopausal women and women in an immunosuppressed state: For LSIL in postmenopausal women, triage can be performed by HPV-DNA testing. For other types of cytologic findings in postmenopausal women, colposcopy and ECC are recommended. colposcopy indications for women with HIV infection and immunosuppressed status after kidney transplantation are the same as for the general population.
4. Women < 21 years of age: For ASC-US in women under 21 years of age, 1 cervical cytology review per year is sufficient. If ASC-US is still present at the 12th month follow-up, it can be reviewed again after 12 months. Colposcopy is required if HSIL or higher grade lesions are found at follow-up. Colposcopy is also required if ASC-US or more advanced lesions are still present at month 24 follow-up.
IV. Management of colposcopic biopsy diagnosis of CIN
The management of colposcopic biopsy diagnosis of CIN includes various physical methods to destroy the involved cervical tissue (cervical freezing, laser, electrocautery, condensation, etc.) and surgical methods to remove part of the cervical tissue (conical hysterectomy, referred to as cervical conization); total hysterectomy cannot be used as the initial treatment for CIN. When choosing treatment measures, in addition to the CIN level, the results of cytologic diagnosis and satisfactory colposcopy should be considered together.
1. Treatment of colposcopic biopsy as CIN1
(1) Cytology reported as ASC-US, ASC-H or LSIL Recommended follow-up observation: HPV can be tested every 12 months or cervical cytology can be repeated every 6 or 12 months. If follow-up reveals HPV positivity or cytology reveals ASC-US or more severe lesions, repeat colposcopy is recommended. If follow-up indicates HPV negativity or two consecutive normal cervical cytologies, patients may return to routine cervical cytology screening. For persistent CIN1 (lasting longer than 2 years), observation may continue or treatment may be given. If treatment is given, it should be selected with reference to satisfactory colposcopy. For patients with satisfactory colposcopy, physical therapy or cervical conization is possible. For patients with unsatisfactory colposcopy, ECC mentioning CIN, or who have been treated for cervical lesions, cervical conization is recommended.
(2) Cytology report of HSIL or AGC recommends cervical conization, especially for unsatisfactory colposcopy. For patients with satisfactory colposcopy and negative ECC, a short observation (1 year) with cytology and colposcopy every 6 months is possible. If HSIL or AGC is still present at the 6th or 12th month follow-up, cervical conization should be performed. If those two consecutive cytologic exams are normal, the patient may return to routine screening.
(3) CIN1 in special populations For CIN1 in adolescent women, 1 cervical cytology screening per year is sufficient. Colposcopy is indicated if lesions above HSIL are still found at the 12th month follow-up or if ASC-US or higher grade lesions are found at the 24th month follow-up. CIN1 in women during pregnancy can be withheld.
2. Management of CIN2 and 3
(1) CIN2 and 3 in the general population For CIN2 and 3 diagnosed by colposcopic biopsy histology, treatment is recommended, not just follow-up observation (except in pregnant women). If colposcopy is satisfactory, both physical therapy and cervical conization are possible (except in pregnant women). If colposcopy is unsatisfactory, cervical conization should be performed. For recurrent CIN 2 and 3, if the patient has fertility requirements, conization can be performed again; if there is no fertility requirement, total hysterectomy is feasible. For follow-up after treatment of CIN 2 and 3, HPV can be tested every 6 months or cytology or cytology combined with vaginal can be performed every 6 months.
Microscopy. If follow-up reveals HPV positivity, or if ASC-US or higher grade lesions are found, a repeat colposcopy is indicated. For patients who are HPV negative, or who have two consecutive positive cytologies, 1 cervical cytology screening per year for the next 20 years is recommended. For patients with positive cervical conization margins, or concurrent ECC findings of CIN 2 or 3, cytology and ECC should be performed 4 to 6 months postoperatively. for patients with positive findings on reexamination, conization should be repeated. If re-conectomy is not possible, total hysterectomy is feasible.
(2) CIN2 and 3 in special populations For CIN2 in adolescent women, follow-up observation is preferred, but treatment can be given. For adolescent women with a clear diagnosis of CIN3 or unsatisfactory colposcopy, treatment should be given. However, if colposcopy is satisfactory, close observation for two years with cytology and colposcopy every 6 months is also possible. If disease progresses during follow-up (cytology reveals HSIL or colposcopy suggests high-grade lesions), repeat biopsies are indicated. If the patient’s two consecutive cytology and colposcopy examinations are normal, the patient may return to routine cervical cytology screening. Treatment is recommended if CIN3 is found again at follow-up or if it persists for more than 24 months.
In pregnant women with a colposcopic biopsy histological diagnosis of CIN 2 or 3, cytology and colposcopy can be repeated every 12 weeks unless there is a high suspicion of invasive carcinoma or the pregnancy is near term and a cervical conization can be considered. If the lesion progresses or suggests invasive carcinoma during follow-up, repeat biopsy may be performed, or treatment may be withheld and postponed until 6 weeks postpartum. In all cases of CIN 2 and 3 detected during pregnancy, the cervix should be re-examined at 6 weeks postpartum.
In summary, the latest ACOG and ASCCP guidelines suggest that cervical cancer cytologic screening should start no earlier than 21 years of age and end at 65-70 years of age; cytologic screening should be performed every 2 years in women 21-29 years of age and every 3 years in women over 30 years of age; HPV-DNA testing has triage value for ASC-US management; colposcopy and ECC should be performed in women with indications women, based primarily on cervical cytologic diagnosis, age, and HPV infection status; colposcopy should include emphasis on satisfactory examination and colposcopically guided multi-point biopsy; management of colposcopic biopsy diagnosis of CIN includes follow-up observation, physical therapy, and cervical conization.