Cervical cancer screening: Benefits, harms, screening methods, and patient risk groups

INTRODUCTION — 

Cervical cancer is common among females worldwide. Most cases occur in resource-limited countries. In resource-abundant countries, large decreases in cervical cancer incidence and mortality rates are related to the availability of primary prevention (with human papillomavirus [HPV] vaccination) and secondary prevention (with screening and subsequent management).

Infection with oncogenic types of HPV (ie, high-risk HPV [hrHPV]) and persistence of hrHPV infection are the most important determinants of progression to cervical cancer. Screening can detect these oncogenic HPV subtypes, as well as precursor lesions (ie, cervical intraepithelial neoplasia [CIN]), and early stage cervical cancers. Treatment of precursors can prevent the development of invasive cervical cancer and reduce cervical cancer morbidity and mortality.

Recommendations for screening, as well as specific screening strategies, balance the benefits of early detection of treatable lesions and reduction in incidence and mortality of cervical cancer with potential risks for false positives, unnecessary procedures, and other harms of over-screening.

This topic will discuss the benefits and harms of screening, describe the available methods of screening (HPV testing, co-testing [with both HPV and cytology], and cytology alone), and define average- and high-risk patient groups.

How to screen for cervical cancer (eg, when to initiate and discontinue screening, frequency of screening) in average-risk patients is described in detail separately. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients".)

Other related topics, including techniques for performing screening tests, interpreting test results, screening patients who are at high risk for cervical cancer, screening in resource-limited settings, and information about invasive cervical cancer, are discussed separately.

●(See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing".)

●(See "Cervical cancer screening: The cytology and human papillomavirus report".)

●(See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states".)

●(See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)

BENEFITS OF SCREENING — 

The benefits of cervical cancer screening in decreasing the incidence, morbidity, and mortality of cervical cancer need to be weighed against the risks of false-positive screening results and subsequent unnecessary procedures.

●Mortality reduction – Multiple observational studies have shown reductions in cervical cancer mortality after the implementation of organized cervical cancer screening programs with systematic follow-up (figure 1) [1-9]. In the United States, mortality due to cervical cancer has continued to decrease since the 1970s (figure 2). Similar trends have been described in other resource-abundant countries (figure 3 and figure 4) [10,11].

Systematic reviews and meta-analyses of observational studies and at least one randomized trial provide evidence that screening leads to a decrease in mortality due to cervical cancer [9,12,13]. However, similar to other screening interventions, the absolute risk reduction for the individual patient is small. Although no randomized trials have been conducted in resource-abundant settings, in a randomized trial of over 130,000 patients in rural India, a single lifetime screen with human papillomavirus (HPV) testing reduced cervical cancer mortality by 50 percent compared with no screening (12.7 versus 25.8 per 100,000 person-years, hazard ratio [HR] 0.52, 95% CI 0.33-0.83) [13]. (See "Screening for cervical cancer in resource-limited settings", section on 'Efficacy'.)

●Decreased incidence of cervical cancer - Systematic reviews, meta-analyses, and observational studies consistently show that screening is associated with a decreased incidence of cervical cancer (figure 2) [9,12,14]. In the randomized trial from India discussed above, a single lifetime screen with HPV testing reduced the number of advanced cervical cancers detected by over 50 percent when compared with no screening (15 per 100,000 person-years with screening versus 32 per 100,000 person-years without screening, HR 0.47, 95% CI 0.32-0.69) [13]. (See "Screening for cervical cancer in resource-limited settings", section on 'Efficacy'.)

●Higher cure rates – Observational studies show that screening is associated with higher cure rates for invasive cervical cancer [15,16]. In a meta-analysis of 12 case-control studies, Pap testing was associated with a decreased risk of subsequent invasive cervical cancer (odds ratio [OR] 0.35, 95% CI 0.3-0.41) [9]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Incidence and mortality'.)

POTENTIAL HARMS

●Patient discomfort and psychosocial consequences – The discomforts and inconveniences of cervical cancer screening are apparent and increase with the frequency and duration of screening; this may be particularly relevant for adolescents and older adults. Screening also has psychosocial consequences. High levels of anxiety are associated with colposcopy referral for patients with high- or low-grade abnormalities as well as with surveillance for mild test abnormalities [17-19]. Anxiety is heightened in patients with a positive human papillomavirus (HPV) test and in younger patients [18,20].

●False-positive results – Both HPV testing and Pap testing are associated with false-positive results that may lead to subsequent diagnostic testing, frequent follow-up examinations, and downstream interventions (eg, loop electrosurgical excision procedure, cold knife conization) which can increase the risk of adverse pregnancy outcomes (eg, second-trimester pregnancy loss, preterm prelabor rupture of membranes, preterm birth) [21]. This is discussed below and in more detail separately. (See 'Relative risks and benefits of each method' below and "Reproductive effects of cervical excisional and ablative procedures".)

SCREENING METHODS — 

Available screening tests include high-risk human papillomavirus (hrHPV) testing, co-testing (with both HPV and cytology), and cytology alone.

It is important to note that screening refers to testing of asymptomatic patients whose prior cervical cancer screening tests were all normal (see 'Average-risk patients' below). Patients who have had prior abnormal results require active surveillance, not "screening," and the recommended options and frequency of such testing differ based on the patient's previous results and underlying risk for developing cervical cancer. Only a minority of such patients will return to routine, age-based cervical cancer screening.

Types of screening and frequency — The various screening methods are as follows:

●Primary HPV testing – With screening using primary HPV testing, an HPV test is performed alone, without cervical cytology; the suggested screening interval for primary HPV testing is every five years. Only certain HPV tests are approved by the US Food and Drug Administration (FDA) for primary hrHPV testing (eg, Alinity, Cobas, Onclarity) (table 1). Many resource-abundant countries (eg, Australia, Netherlands, United Kingdom) have transitioned to nationwide organized screening with this method.

FDA-approved tests for HPV genotyping have the ability to perform genotyping for HPV types 16 and 18 (which are associated with the highest risk of cervical intraepithelial neoplasia and cancer). Extended genotyping allows for identification of additional HPV groups (beyond 16 and 18) to provide additional risk stratification (table 2) and help guide management. This is discussed in more detail elsewhere. (See "Cervical cancer screening: Risk assessment, evaluation, and management after screening", section on 'Terminology and incidence' and "Cervical cancer screening: Risk assessment, evaluation, and management after screening", section on 'HPV positive, genotyping performed'.)

Only deoxyribonucleic acid (DNA)-based methods are approved for primary HPV testing. However, ribonucleic acid (RNA)-based methods may be as effective as DNA-based methods in detecting cervical disease and are approved for co-testing with cervical cytology. In a meta-analysis evaluating the accuracy of different screening methods for detecting cervical intraepithelial neoplasia (CIN) 2+ in clinician-obtained samples, testing with RNA compared with DNA-based assays had similar sensitivity and specificity, though internal controls for specimen adequacy were not available for most assays [22]. Sensitivity was lower for self-collected samples (0.84, 95% CI 0.74–0.96). Further studies evaluating RNA-based methods for primary HPV testing are needed.

•Role of self-collection – Self-collection is a type of primary HPV testing with a suggested screening interval of every three years [23].

Self-collection may be useful for patients with barriers to screening (eg, patients with limited access to health care, gender minority patients, patients with a history of abuse/trauma, patients with physical disabilities), or may be preferred by some patients [24,25]. In the United States, only certain HPV tests have been approved by the FDA for self-collection (table 1); self-sampling devices are also available in other resource-abundant countries, such as the Netherlands and Australia [26,27] and in some resource-limited settings. This is discussed in more detail elsewhere. (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing", section on 'Cervical testing' and "Screening for cervical cancer in resource-limited settings", section on 'Self-collected samples' and "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'Role of HPV self-collection'.)

●Co-testing – In co-testing, both cytology and HPV test are collected, and results are provided concurrently; the suggested screening interval for co-testing is every five years. There are many tests that are approved by the FDA for co-testing (table 1). However, co-testing results in a doubling of tests being performed (Pap and HPV testing) and therefore may not be sustainable in all settings.

A United States Preventive Services Task Force (USPSTF) review of four randomized trials found a similar number of detected cancer cases with co-testing at a frequency of every five years compared with Pap testing alone every three years, although differences in study methodology (colposcopy referral methods and thresholds) made interpretation complex [28].

●Reflex HPV testing (also called triage HPV testing) – Reflex HPV testing is performed when a cervical cytology result returns positive for atypical squamous cells of undetermined significance (ASC-US); the HPV test is automatically performed on the sample that was collected for the cervical cytology.

●Cytology alone – In Pap testing, cervical cytology is performed to assess for cellular abnormalities; the suggested screening interval for Pap testing alone is every three years.

The incidence of high-grade cytologic abnormalities is very low within three years of a normal Pap test (10 to 66 per 10,000) [29], and modeling studies have suggested cancer detection rates to be similar with annual or triennial screening, while doubling or tripling the number of downstream interventions, including colposcopies with annual screening [30-32]. A synthesis of several studies in patients aged 21 to 29 years predicted that the lifetime risk of death due to cervical cancer would be similar: 0.03, 0.05, and 0.05 per 1000 patients with screening annually, every two years, and every three years, respectively [33].

The screening intervals noted above apply only to patients with normal results. Management of patients with abnormal cervical cancer screening results is discussed separately. (See "Cervical cancer screening: Risk assessment, evaluation, and management after screening".)

Society guidelines regarding the age to initiate and discontinue screening and which testing method is used are presented separately. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'Testing method and frequency'.)

Relative risks and benefits of each method

●Mortality reduction – There are no randomized trials comparing mortality rates among the various screening strategies in the United States. However, a microsimulation model for the USPSTF found that screening strategies that included HPV testing (ie, primary HPV testing or co-testing) were associated with fewer cervical cancer deaths compared with screening strategies that included Pap testing (ie, Pap testing alone or reflex HPV testing). In this model, cervical cancer deaths associated with screening that included HPV testing ranged from 0.23 to 0.29 deaths per 1000 patients versus 0.3 to 0.76 deaths per 1000 patients with screening that included Pap testing [34].

●Cervical disease detection and incidence – HPV testing has been shown to be a very sensitive test for identifying potential precursors of cervical cancer during an initial round of screening [12,35-39] and decreases the incidence of cervical cancer (by allowing for precursor lesions to be identified and treated) [39-47].

•In a systematic review including eight randomized trials and five cohort studies for the USPSTF, primary HPV screening among patients ages 25 to 65 years was associated with increased detection of CIN 3+ compared with Pap testing alone in the initial round of screening (relative risk [RR] range 1.6 [95% CI 1.1-2.4] to 7.5 [95% CI 1-54.7]; four trials) [48]. The RR of CIN 2+ was also lower with primary HPV testing than with initial Pap testing. By contrast, co-testing did not increase the initial CIN3+ detection rate compared with Pap testing alone.

•In a subsequent randomized trial in Sweden of over 395,000 females ages 30 to 64 years, those undergoing primary HPV screening with cytology triage (54 percent) compared with cytology screening with HPV triage had fewer cervical cancers (257 versus 266 cervical cancers; HR 0.83, 95% CI 0.7-0.98) over the eight-year follow-up period [49]. In addition, the incidence of cervical cancer was approximately seven times lower in those with a baseline negative HPV test compared with a baseline negative cytology test (1.3 versus 9.1 per 100,000 person-years). The lower risk of cervical cancer in the HPV group is likely due to the earlier detection of cervical cancer precancers (CIN 2+).

•In an earlier large European meta-analysis, screening with HPV testing (largely as co-testing) was associated with a lower rate of incident cervical cancer compared with Pap testing at a median of 6.5 years of follow-up (rate ratio 0.6, 95% CI 0.4-0.89) [47].

●False-positive and colposcopy rates – Studies have found that primary HPV testing is associated with an increased number of positive results compared with cervical cytology [12,27,35,48,50-53]. This is due, in part, to the fact that HPV often regresses, and it is only persistent high-risk HPV positivity or infection with one of the highest-risk HPV subtypes that results in precancers or cancers. Thus, in such cases, HPV infections identified during screening may lead to unnecessary procedures (eg, colposcopy, biopsy, treatment), particularly in younger patients in whom HPV infection often regresses. With the increased utilization of extended HPV genotyping, and attention to quality colposcopy, the efficiency of screening improves. (See 'Types of screening and frequency' above and "Colposcopy", section on 'Effectiveness'.)

In the USPSTF systematic review comparing HPV testing with cytology alone discussed above, during first-round screening, there was an increase in false-positive rates with primary HPV testing (6.6 to 7.4 percent) compared with cytology alone (2.6 to 6.5 percent) [48]. For co-testing, false-positive rates were also higher (5.8 to 19.9 percent).

In modeling studies of screening at various time intervals, decreasing the frequency of screening is associated with a decrease in colposcopy rates. In one modeling study of patients >30 years, a combination of Pap and HPV testing every five years was as effective as screening with Pap testing alone every three years [28]. In another modeling study of patients aged 40 years, co-testing every five years was associated with decreased colposcopies compared with co-testing every three years, with only a minimal change in lifetime cancer risk (0.39 versus 0.61 percent) [54].

False-positive results can also lead to potential psychosocial consequences (eg, anxiety). This is discussed above. (See 'Potential harms' above.)

Role of single lifetime screening — World Health Organization guidelines state that screening even once in a lifetime is beneficial; decisions about the target age, type, and frequency of screening depend on the local burden of disease, costs, and infrastructure (eg, availability of reliable transportation and/or medical equipment and supplies) and are left to country-level decision-makers [55]. This strategy may be particularly relevant in resource-limited settings and is discussed in detail elsewhere. (See "Screening for cervical cancer in resource-limited settings", section on 'Screening age and frequency'.)

Impact of organized screening systems — There are two kinds of screening systems: organized and opportunistic screening systems [56].

In organized screening systems, nationally funded healthcare programs utilize databases to systematically identify and invite individuals due for screening. Examples of countries with such systems include the United Kingdom, Sweden, and Australia. By contrast, in other countries (the United States is an example), screening is "opportunistic" and, given the absence of a national organized health care program, lacks a formal invitation process. Individuals in such settings rely on their health care provider to recommend a screening test, often during an encounter for another indication or annual examination.

Given centralized oversight, and because there is typically little or no cost to participants, countries with organized screening systems are often able to increase screening uptake and ensure proper follow-up [57].

PATIENT GROUPS — 

Cervical cancer screening recommendations differ for various patient groups; these groups are defined below.

Average-risk patients — Screening recommendations for patients who are at average risk for cervical cancer apply to patients with a cervix who have all the following:

●Asymptomatic (ie, no signs or symptoms of cervical disease such as abnormal bleeding).

●Immunocompetent.

●Have had all normal cervical cancer screening results in the past. The only situations in which patients are at sufficiently low risk to return to age-based routine screening are the following [21]:

•Patients age <25 years with human papillomavirus (HPV)-negative atypical squamous cells of undetermined significance (ASC-US)

•Patients age <25 years with low-grade squamous intraepithelial lesions (LSIL) or HPV-positive ASC-US, followed by two consecutive negative cytology results.

•Patients age >25 years with LSIL followed by colposcopy in which cervical intraepithelial neoplasia (CIN) 2 or worse was not found and followed by three consecutive negative co-testing results.

•Patients ≥25 years with HPV-negative ASCUS followed by a negative HPV test or co-test.

Recommendations for what ages to initiate and discontinue screening and which screening method to choose are described separately. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'How to screen'.)

High-risk patients — Screening recommendations for patients who are at high risk for cervical cancer apply to patients with any of the following:

●HIV or immunosuppression – Patients with HIV and those without HIV who are on long-term immunosuppressive therapy (eg, solid organ transplant, allogeneic hematopoietic stem cell transplant, systemic lupus erythematous, and those with inflammatory bowel disease or rheumatologic disease requiring current immunosuppressive treatments) are at an increased risk of developing high-grade cervical dysplasia and cervical cancer [58-64]. Recommendations for what ages to initiate and discontinue screening and which screening method to choose are described separately. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states".)

By contrast, patients with inflammatory bowel disease or rheumatoid arthritis not actively on immunosuppressive therapy may not be at higher risk for cervical cancer, but this has not been well studied. Such individuals are screened using the above guidance for average-risk patients. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'How to screen'.)

●DES-exposed individuals – Patients with a history of diethylstilbestrol (DES) exposure in utero may also be at higher risk of cervical cancer and thus may be screened differently than average-risk patients. This is also discussed separately. (See "Outcome and follow-up of diethylstilbestrol (DES) exposed individuals".)

The term high risk does not apply to patients with a history of abnormal cervical cancer screening, as such patients are managed with active surveillance, not screening. Surveillance of such patients depends on the screening abnormality, which is discussed separately. (See "Cervical cancer screening: Risk assessment, evaluation, and management after screening" and "Cervical cytology: Evaluation of atypical and malignant glandular cells" and "Cervical intraepithelial neoplasia: Management".)

Recipients of HPV vaccine — The optimal approach to cervical cancer screening in patients who have received the HPV vaccine remains uncertain [65]. Until data from clinical trials are available, current standard cervical cancer screening recommendations should be observed for patients who have received the HPV vaccine [28,33,66-69]. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'Recipients of HPV vaccine'.)

HPV vaccination of female and male adolescents reduces the risk of developing cervical dysplasia [70,71]. However, the vaccine does not provide immunity against all HPV types responsible for cervical cancers, and some vaccine recipients may already be infected with high-risk HPV [68]. (See "Human papillomavirus vaccination".)

HPV vaccination may lower the positive predictive value (PPV) of cervical cytology in predicting CIN, although further data are needed. In a prospective cohort study of over 150,000 patients (20,000 of whom had abnormal cervical cytology), the PPV of abnormal cytology for CIN 2+ was lower in HPV-vaccinated patients (57 to 65 percent, depending on age of vaccination) compared with unvaccinated patients (70 percent) [72]. Lower PPVs were also noted for patients with low-grade cervical lesion.

Further discussion about HPV vaccination in patients with CIN and management of sexual partners can be found elsewhere. (See "Cervical intraepithelial neoplasia: Management", section on 'Candidates for HPV vaccination'.)

Symptomatic patients — Patients who have signs or symptoms of cervical disease (eg, abnormality on visualization or palpation of the cervix, abnormal or postmenopausal bleeding, abnormal discharge, pelvic pain, or change in bowel or bladder function) should undergo appropriate diagnostic evaluation regardless of prior screening history. Diagnostic testing typically includes a Pap test with colposcopy and cervical biopsies By definition, this diagnostic evaluation is not "screening" and may require additional follow-up. (See "Colposcopy" and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

IMPROVING SCREENING RATES — 

More than one-half of patients who develop cervical cancer have not been screened adequately; among patients diagnosed with invasive cervical carcinoma, one-half have never had a Pap test and another 10 percent have not had a test in the past five years [73-76].

In a survey of screening in the United States in 2018, 83 percent of patients with a cervix ages 21 to 65 years reported having had a Pap test within the preceding three years or co-testing within five years [77]. Never-screened and under-screened patients tend to be older patients and those with no usual source of health care, the uninsured, and patients who immigrated to the United States within the past 10 years [78-80]. In Canada, screening rates are low in patients with disability and those with chronic conditions [81]. Globally, patients exposed to natural disasters (including the coronavirus disease 2019 [COVID-19] pandemic) experience disruptions in health care and may have lower screening rates [82,83].

Screening may also be lower in HPV-unvaccinated patients. In one United States survey in 2019 including over 4500 patients (ages 21 to 39), more unvaccinated compared with vaccinated patients had never received screening (21 to 29 years: 32 versus 18 percent; 30 to 39 years: 13 versus 5 percent) [84].

Various strategies can be used to increase screening rates.

●Actively inviting patients to schedule an appointment for cervical cancer screening is an effective way to increase participation in a screening program [85], though even active solicitation resulted in <20 percent increase in screening in one systematic review [86]. The most effective single intervention used a dedicated nurse practitioner and offered same-day screening (33 percent increase in screening) [86].

●Urgent care or emergency department (ED) visits can be used as an opportunity to screen patients who are unlikely to otherwise comply with cervical cancer screening recommendations [87]. In one single-arm intervention pilot study including 119 eligible patients in an ED waiting room who were overdue for cervical cancer screening, >90 percent accepted an HPV self-collection kit and performed testing prior to leaving the ED [88]. However, as patient follow-up in this setting can be difficult (and an abnormal screening result requires additional follow-up), this option is not often utilized.

●Initiating a reminder system is helpful for ensuring compliance with follow-up [89]. A systematic review of 70 randomized trials of interventions to promote screening for cervical cancer found good evidence that invitation letters can increase cancer screening uptake, and more limited evidence that educational interventions are also effective [90]. In some areas where approved, self-sampling for HPV can fill gaps of care for cervical cancer screening.

"Over-screening" is also a concern, primarily due to initiating screening at an earlier age, or discontinuing screening at a later age than recommended [91,92]. In one cohort study including more than 2.2 million commercially insured patients in the United States at average risk for cervical cancer, nearly two-thirds of patients were over-screened (ie, had repeat testing at intervals less than three years); over-screened patients were younger (age 30 to 39 years versus 60 to 64 years), without comorbidities, and screened with Pap testing alone [93]. (See "Cervical cancer screening: The cytology and human papillomavirus report", section on 'Special considerations'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cervical cancer screening, prevention, and management".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Cervical cancer screening tests (The Basics)")

●Beyond the Basics topics (see "Patient education: Cervical cancer screening (Beyond the Basics)" and "Patient education: Management of a cervical biopsy with precancerous cells (Beyond the Basics)" and "Patient education: Follow-up of low-grade abnormal Pap tests (Beyond the Basics)" and "Patient education: Follow-up of high-grade or glandular cell abnormal Pap tests (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Screening rational – For all patients with a cervix, we recommend screening for cervical cancer (Grade 1B). Cervical cancer screening leads to a decrease in the incidence, morbidity, and mortality of cervical cancer (figure 2). Even single lifetime screening is associated with a reduction in mortality. However, since the absolute risk reduction for an individual patient is small, and positive results may lead to unnecessary procedures in some patients, some individuals may elect to be screened at less frequent intervals or not at all. (See 'Benefits of screening' above and 'Potential harms' above and 'Role of single lifetime screening' above.)

●Types and frequency of screening – Screening methods and frequency for average-risk patients include (see 'Types of screening and frequency' above):

•Primary human papillomavirus (HPV) testing – Primary HPV testing is performed every five years (clinician-collected sample) or three years (self-collection); many resource-abundant countries have transitioned to screening with this method.

-Only certain HPV tests are approved by the US Food and Drug Administration (FDA) for primary high-risk HPV (hrHPV) testing (eg, Alinity, Cobas, Onclarity) (table 1).

-Self-collection of HPV samples may be useful for patients with barriers to screening (eg, patients with limited access to health care, gender minority patients, patients with a history of abuse/trauma, patients with physical disabilities) or be preferred by some individuals. In the United States, only certain HPV tests have been approved by the FDA for self-collection (table 1).

•Co-testing – Co-testing (HPV and cytology) is performed every five years.

•Cytology alone – Cytology alone is performed every three years.

●How to screen – How to screen (ie, the age to initiate and discontinue screening, which testing method to use) is presented separately. (See "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients", section on 'Testing method and frequency'.)

●Patient groups

•Average risk – Patients who are at average risk for cervical cancer include those with a cervix who are asymptomatic (ie, no signs or symptoms of cervical disease such as abnormal bleeding), immunocompetent, and have had all normal cervical cancer screening results in the past, with a few exceptions, as noted above. How to screen such patients (ie, age to initiate and discontinue screening and which testing method is used) is discussed separately. (See 'Average-risk patients' above and "Cervical cancer screening in resource-abundant settings: How to screen average-risk patients".)

•High risk (see 'High-risk patients' above)

-Patients with HIV and those without HIV who are on long-term immunosuppressive therapy are at an increased risk of developing high-grade cervical dysplasia. This is discussed in detail separately. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states".)

-Patients with a history of diethylstilbestrol (DES) exposure in utero may also be at higher risk of cervical cancer and thus may be screened differently than average-risk patients. This is also discussed separately. (See "Outcome and follow-up of diethylstilbestrol (DES) exposed individuals".)

-The term high risk does not apply to patients with a history of abnormal cervical cancer screening, as such patients are managed with active surveillance, not screening. Surveillance of such patients depends on the screening abnormality, which is discussed separately. (See "Cervical cancer screening: Risk assessment, evaluation, and management after screening" and "Cervical cytology: Evaluation of atypical and malignant glandular cells" and "Cervical intraepithelial neoplasia: Management".)

•Symptomatic patients – Patients who have signs or symptoms of cervical disease (eg, abnormality on visualization or palpation of the cervix, abnormal bleeding, abnormal discharge) should undergo appropriate diagnostic evaluation (with Pap testing, colposcopy, and/or cervical biopsies), not "screening." (See 'Symptomatic patients' above.)

●Improving screening rates – More than one-half of patients who develop cervical cancer have not been screened adequately. Various strategies (eg, actively inviting patients to schedule an appointment for cervical cancer screening, initiating a reminder system) can be used to increase screening rates. (See 'Improving screening rates' above.)