2016 ACOG Cervical Cancer Screening and Prevention (I)
In January 2016, the American College of Obstetricians and Gynecologists (ACOG, American College of Obstetricians and Gynecologists) published practice guidelines for screening and prevention of cervical cancer (ACOG Practice Bulletin No. 157, ObstetGynecol. 2016;127:185-7.) to replace Practice Guideline No. 131, which was published in November 2012.The ACOG practice guidelines focus on the latest in various areas of practical obstetric and gynecologic care The ACOG practice guidelines are a summary of the latest technical and clinical treatment information in all areas of practical OB/GYN care. These practice guidelines and clinical management recommendations are based on a large body of evidence, and the ACOG is the premier professional society for the protection and treatment of women’s health in the United States, with 58,000 members. Thanks to widespread cervical cancer screening, the incidence of cervical cancer in the United States has decreased by more than 50% in the last 30 years: from 14.8 cases per 100,000 women in 1975, the incidence rate dropped to 6.7 in 2011, and the mortality rate dropped simultaneously from 5.55 to 2.3 cases per 100,000 women. ASCCP) and the American Society for Clinical Pathology (ASCP) updated cervical cancer screening guidelines in 2011 (Saslow D, et al. CA Cancer J Clin 2012;62:147C72), followed by updated screening guidelines from the U.S. Preventive Services Task Force (USPSTF) (Moyer VA. Ann Intern Med 2012;156:880C91).
In April 2014, the U.S. Food and Drug Administration (FDA) approved the Roche HPV test for primary screening for cervical cancer; in February 2015, the ASCCP and 14 experts from the Society of Gynecologic Oncology (SGO) issued an interim recommended guideline on HPV testing in cervical cancer screening (Huh WK et al. ObstetGynecol 2015;125:330C7). Clinicians and patients in the United States are now left with the complex or puzzling question of what protocol to adopt for cervical cancer screening in the midst of new technologies and methods, and whether HPV testing can replace cytologic screening. The ACOG 157 practice guideline provides a very comprehensive summary of the history and current status of cervical cancer screening and prevention for women in the United States, the application and development of cervical cytology, the progressive revision of the cytology TBS report, the application of high-risk HPV testing and HPV genotyping in cervical cancer screening, and a review of the use of cytology and HPV genotyping in cervical cancer screening. revision of clinical management guidelines for women with abnormal HPV tests, etc.
We have translated the full text of ACOG 157 Practice Guideline, and due to the limitation of chapter length, it is published in 3 parts consecutively, and we appreciate your criticism and correction for any deficiencies. Those who are interested are highly recommended to read the full text.
Over the past 30 years, the incidence of cervical cancer has decreased by more than 50% due to the widespread use of cervical cytology screening in the U.S. In 1975, the incidence rate was 14.8 cases per 100,000 women. By 2011, the rate had decreased to 6.7 cases per 100,000 women. The death rate from the disease has decreased to a similar degree, from 5.55 per 100,000 women in 1975 to 2.3 deaths per 100,000 women in 2011. The American Cancer Society (ACS) estimates that there will be 12,900 new cases of cervical cancer and 4,100 deaths from the disease in the United States in 2015. Cervical cancer is common worldwide, especially in unscreened countries, with an estimated 527,624 new cases and 265,672 deaths from the disease each year. Once cervical cancer screening was introduced into the community, there was a significant decline in the incidence of cervical cancer.
New techniques for cervical cancer screening are constantly being improved, and therefore clinical management recommendations are constantly being updated. In addition, recommendations for women of different ages are reflected in screening guideline protocols, taking into account the pros and cons of different age groups. In 2011, joint guidelines for cervical cancer screening were updated by the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP), and updated recommendations from the U.S. Preventive Services Task Force (USPSTF) were published. Subsequently, in 2015, the ASCP and the Society of Gynecologic Oncology (SGO) published an interim guideline on human papillomavirus (HPV) testing as primary screening for cervical cancer that was approved by the U.S. Food and Drug Administration (FDA) in 2014. The purpose of this article is to provide a review of the best evidence for cervical cancer screening.
Background
Most cervical cancers occur in women who have never been screened or are inadequately screened. One study estimated that 50% of patients with cervical cancer never undergo cervical cytology and an additional 10% are not screened in the 5 years prior to diagnosis. Providing additional public health measures is important to improve screening because these women are often uninsured or underinsured. Although the incidence of cervical cancer is decreasing for U.S.-born women with access to screening, women who immigrate to the United States, lack formal health care resources, or are uninsured are still at higher risk.
The natural history of cervical neoplasia
Human papillomavirus (HPV) is divided into 2 categories: 1) oncogenic and 2) non-oncogenic. Infection with oncogenic (or high-risk) HPV is a necessary but not sufficient condition for the development of cervical intraepithelial neoplasia. Therefore, only a small percentage of women infected with HPV will develop severe cervical lesions or cervical cancer. Cervical cancer is currently thought to occur as a result of HPV infection, which can be transient or persistent. Most HPV infections are transient and have a low risk of progression. Only a small proportion of infections are persistent, but persistent infection for 1 and 2 years strongly predicts the risk of progression to CIN 3 or cervical cancer, regardless of age.
HPV genotyping appears to be the most important determinant of persistent HPV infection and lesion progression in the cervix. HPV-16 has the strongest oncogenic potential and is associated with approximately 55-60% of all cervical cancer cases worldwide; HPV-18 is second, with 10-15% of patients associated with it. The remaining cervical cancers are associated with approximately 12 additional HPV subtypes. Co-factors known to contribute to persistent HPV infection include smoking, immune system deficiency, and HIV infection. HPV infection is often seen in adolescents and women in their 20s, with infection rates decreasing with age. Most young women, especially those younger than 21 years, are able to clear HPV infection through an effective immune response within an average of 8 months, or 85-90% of women have reduced their viral load to a negative test within 8-24 months. In this population, most cervical lesions regress spontaneously as the infection clears.
For women aged 30-65 years, the natural course of HPV infection does not change with age. For women 30 years of age and older, persistent infection after new HPV infection is unlikely. However, women older than 30 years of age are more likely to present with persistent infection. This is consistent with the increasing incidence of high-grade squamous intraepithelial neoplasia (HSILs) with increasing age.
Considering that low-grade cervical lesions (or CIN1), a manifestation of acute HPV infection, have a high probability of regression to normal tissue, it is recommended that expectant treatment is feasible. In contrast, the clinical management of CIN2 is currently controversial, and the problem lies in the difficulty of accurate diagnosis and ideal treatment. The prognosis of CIN2 appears to be a mixture of low- and high-grade lesions, which are difficult to distinguish simply by histology, rather than just being a separate intermediate lesion. Considering the limitations of the CIN2 classification, the ASCCP and the American Academy of Pathology adopted a revised 2-level histologic classification (low-grade squamous intraepithelial lesions (LSILs] and HSILs), eliminating CIN2 as a separate classification. In a cohort study of untreated CIN3 patients, the cumulative incidence of 30-year invasive cervical cancer was 30.1%, indicating that CIN3 is at great risk of progression to cancer.
The time required for disease progression needs to be considered when assessing the appropriate screening interval. Most HPV-associated cervical lesions progress very slowly, and the exact time to progression from CIN 3 to cancer is not known, but the time to progression from CIN 3 to cancer at different ages of diagnostic screening is 10 years showing that precancerous status is a very long process. Therefore, less frequent screening (at least one year interval) is appropriate for this slower disease process.
Cervical cytology screening techniques
Both liquid-based and conventional methods of cervical cytology specimens can be used for screening. Exfoliated cells are collected from the cervical migratory zone, transferred to a liquid storage solution and processed in the laboratory (liquid-based cytology technique), or transferred directly to a slide and fixed (conventional technique). Blood, secretions and lubricants (including those used by the patient herself) may interfere with the interpretation of the sample. The use of a small amount of aqueous lubricant on the vaginal speculum can significantly reduce discomfort during examination compared to water alone (45C47). At least one manufacturer has produced a list of lubricants that do not contain interfering substances. If an aqueous lubricant is used, reduce the amount it touches the cervix and choose a water-based lubricant that matches the manufacturer’s recommended liquid-based kit. Small amounts of water-based lubricant on the vaginal speculum did not diminish cervical cytology. four published randomized controlled trials assessing the effect of lubricant on conventional cytology showed no effect on cervical cytology results. Large amounts of lubricant applied directly to the cervix (e.g., 1-1.5 cm thick lubricant applied directly to the cervical os) can affect specimen volume, but this is not a standard clinical procedure. In a retrospective study of 4,068 specimens from liquid-based cytology Pap tests, 0.4% had ambiguous material, which could lead to misinterpretation of the results, half of which could be related to the lubricant.
The advantage of specimen collection in the liquid-based cytology method is that it allows a single specimen to be used for cytology and HPV testing to detect gonorrhea and chlamydial infection. Despite the theoretical advantages of liquid-based techniques, such as ease of interpretation, filtration of blood and debris, and fewer unsatisfactory results, a meta-analysis of eight studies and one randomized trial showed that liquid-based cytology techniques did not outperform traditional cytologic screening techniques in terms of sensitivity and specificity for detecting CIN.
Reporting of cytologic results
Widely accepted in the United States is the TBS report of cervical cytology. It has been revised three times since 1988.
Box 1. 2014 Cervical Cytology Reporting Bethesda System
Specimen type.
Refers to: conventional examination (Pap smear), liquid-based cytology, or other.
Quality of specimen.
Satisfactory assessment (describe the presence of a cervical canal/cervical migration zone component, and other quality criteria, such as partial visible bleeding, inflammation, etc.)
Unsatisfactory assessment (indicate reasons)
- Specimen rejected or unprocessed (indicate why)
- Sample was processed and tested but was unsatisfactory for assessment of epithelial abnormalities (indicate reason)
General classification (optional)
No intraepithelial lesions or malignant lesions seen
Other: see explanation/results (e.g., endothelial cells in women 45 years of age or older)
Abnormal epithelial cells: see interpretation/results (clearly “squamous” or “glandular”)
Interpretation/results
No intraepithelial or malignant lesions seen (if no cytologic evidence of neoplasia is present, the interpretation/results section of the report states whether pathogenic or other non-neoplastic findings are present in the general classification above.
—Non-neoplastic findings ((may be selectively reported; need not be listed in full)
Non-neoplastic cellular changes
Squamous epithelial metaplasia
Keratinizing changes
tubal epithelial metaplasia
atrophy
Pregnancy-related changes
Reactive cellular changes associated with
inflammation (including typical repair)
Lymphocytic (follicular) cervicitis
Radiation
intrauterine device (IUD)
Status of glandular cells after hysterectomy
Pathogenic bacteria
Trichomonas vaginalis
Fungal microorganisms, morphologically consistent with Candida spp.
Altered flora suggestive of bacterial vaginosis
Bacterial morphology consistent with Actinomyces spp.
Altered cell morphology consistent with herpes simplex virus infection
Altered cell morphology consistent with cytomegalovirus infection
Other
–Endometrial cells (in women 45 years or older) (specify if “no squamous intraepithelial lesions”)
Abnormal epithelial cells
Atypical squamous cells (ASC)
of undetermined significance (ASCUS)
HSIL cannot be excluded (ASC-H)
Low grade squamous intraepithelial lesion (LSIL) (including: HPV/mild hyperplasia/cervical intraepithelial neoplasia CIN1)
High grade squamous intraepithelial neoplasia (HSIL) (including: moderate to severe hyperplasia, carcinoma in situ; CIN2 and CIN3)
Suspicious infiltration (when infiltration is suspected)
Squamous cell carcinoma
–Glandular epithelial cells
Atypical glandular epithelial cells
Cervical duct cells (not otherwise specified, or indicated in the commentary)
Endothelial cells (not otherwise specified, or as noted in the commentary)
Glandular cells (not otherwise specified, or as noted in the notes)
Atypical glandular epithelial cells
Cervical duct cells, tumor-prone
Adenocytes, tumor-prone
adenocarcinoma in situ of the cervical duct
Adenocarcinoma
Cervical duct
Endometrium
Ectopic uterus
Not otherwise specified
Other malignant neoplasm (to be indicated)
Ancillary examinations
A short description of the examination methods and reported results to make it easy for clinicians to understand.
Computer-assisted cervical cytology
If the examination was performed using automated equipment, indicate the equipment and results.
Delivery of notes and instructions to be attached to the cytology report (optional)
Recommendations should be concise and consistent with clinical follow-up guidelines issued by professional organizations (refer to relevant publications)
Human papillomavirus testing
Several methods have been approved by the US FDA for the detection of cervical HPVDNA. They can detect 15-18 HPV subtypes that have a potential carcinogenic risk (high-risk type) in cervical exfoliated cells. Most of the 13-14 subtypes detected are also the most common high-risk subtypes. These kits should be used correctly according to the FDA-approved scope of application and meet the criteria for clinical examination. Liquid-based cytology and HPV testing are specific sample collection methods approved by the U.S. Food and Drug Administration (FDA). Only FDA-approved ones should be used for HPV testing, as unapproved ones may provide false results under certain conditions. indications for HPV testing are
For women with cytologic ASCUS, to determine the need for colposcopy (triage)
For women 30-65 years of age or older, screening for cervical cancer along with cytology (combined screening).
The HPV test was approved by the FDA in 2014 for primary screening for cervical cancer in women 25 years of age and older.
The test can only be used for detection of high-risk HPV viruses. Testing for low-risk HPV is not meaningful and therefore should not be performed for low-risk HPV viruses. The references for HPV testing in this article are for high-risk HPV. some major societies’ guidelines also include some non-indications for use, such as post-treatment follow-up. These nonindications should be used strictly in accordance with these major societies’ guidelines.
HPV Typing
Two commercially available FDA-approved HPV tests are available for HPV-16, HPV-18, or a combination of both. Guidelines support the use of HPV typing tests in women aged 30-65 years who undergo combined cytology and HPV screening and who test negative for Pap tests and positive for high-risk HPV types.
HPV vaccine
The currently introduced vaccine against the most common oncogenic HPV subtypes has led to improved basic prevention of cervical cancer. In Australia, there is a population-based vaccination program with high adherence and an effective reduction in the incidence of high-grade cervical lesions within 3 years of program implementation. three FDA-approved vaccines have been shown to be effective in preventing HPV infection: (1) bivalent vaccine, which includes HPV-16 and HPV-18; (2) quadrivalent vaccine, which includes HPV-6 and HPV-18 in addition to HPV-16 and HPV-18; and (3) quadrivalent vaccine, which includes HPV-6 and HPV-18. 18, HPV-6 and HPV-11; and (3) the nine-valent vaccine approved in 2014, which covers five additional high-risk HPV subtypes. The bivalent and quadrivalent vaccines have limited cross-protection against the approximately 30% of cervical cancers caused by non-HPV-16 and 18 subtypes. The nine-valent vaccine covers more than 20% of infections with high-risk HPV types caused by the other five HPV subtypes. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP, advisory committee on immunization practices), and the American College of Obstetricians and Gynecologists (ACOG) recommend the vaccine for women aged 9-26 years. For adults and adolescents with opportunistic HIV infection, the working group recommends vaccination at ages 9-26. The Working Group and ACIP recommend vaccination before girls may have HPV exposure. However, more women prefer to be vaccinated older or after viral exposure. It is estimated that a significant reduction in cervical cancer incidence may not be seen until 20 years after widespread vaccination. For now, cervical cancer screening remains the best way to protect women from cervical cancer, and screening is being done without considering HPV vaccination for now.
Revaccination with the nine-valent HPV vaccine is not routinely recommended after completion of the previous three-dose series of the quadrivalent HPV vaccine or the bivalent vaccine. If a female patient has already started HPV vaccination, she can complete any HPV vaccine product in this series (66). Therefore, given the high protective effect of HPV vaccine versus the risk of infection in unvaccinated women, it is recommended that eligible patients should receive any vaccine that is readily available and should not delay getting a specific type of vaccine.
Weighing the benefits and risks in cervical cancer prevention
Prevention of cervical cancer is the primary purpose of screening, but as the prevalence of the disease decreases, other considerations become equally important in the decision-making process. For example, invasive diagnostic tests (e.g., colposcopy and biopsy), the adverse consequences of overtreatment of lesions that may regress spontaneously, such as increased costs, and the potential to affect reproductive outcomes. In addition, the anxiety and aggravation caused by HPV infection in women who attend cervical cancer screening is equally worrisome.
Cervical cancer screening guidelines have been corrected several times over the past decade, and the differences in lifetime risk of disease associated with cervical cancer screening strategies based on them have not been significant. Because most cervical cancers detected by screening are at an early stage, their survival rates are so high that their average life expectancy varies much less between screening methods. The current revised version combines the predictive value of a negative HPV test with an extended screening interval to provide a good balance of the pros and cons of cervical cancer screening. The current guidelines are based on achieving a baseline value for cancer risk through cervical cytology screening every 3 years. Cancer risk can be reduced through frequent screening, but requires more diagnostic evaluation, more inconvenience to patients, increased costs and other harms of screening. The interval of screening needed to properly weigh the pros and cons is still up for discussion. Informing patients of the benefits and potential harms of screening will aid clinical decision making and will take full account of patient wishes.