Cervical Cancer Screening in Menopause: When Is It Safe to Exit?

Margaret E. Long, MD; Yeonsoo S. Lee, BS; Suneela Vegunta, MD

Menopause. 2023;30(9):972-979.

Abstract and Introduction

Abstract

Importance and Objective: Despite a decreasing incidence of cervical cancer in North America overall, disparities in screening and cervical cancer rates persist, especially in the postmenopausal age group.

Methods: We reviewed the literature regarding cervical cancer screening considerations for postmenopausal persons, with a focus on cervical cancer in postmenopausal persons, existing guidelines, screening methods, and gaps in care.

Discussion and Conclusion: Postmenopausal persons are an important population at risk because age 65 years in the United States and up to 70 years in some parts of Canada is a milestone for screening cessation if the criteria are met. Unfortunately, inadequate screening is common, with most women 65 years or older discontinuing (exiting) screening despite not meeting the criteria to do so. Screening cessation recommendations are nuanced, and if not all criteria are met, screening should be continued until they are. Cervical cancer screening should be stopped at the recommended age if adequate screening has occurred or at any age if life expectancy is limited or the patient has had a hysterectomy in the absence of high-grade preinvasive cervical lesions or cervical cancer. Human papillomavirus infection, which is causally linked to almost all cervical cancer cases, can persist or reactivate from a prior infection or can be newly acquired from sexual contact. With more persons aging with a cervix in place, the potential for cervical cancer has increased, and higher cancer rates may be observed if recommended screening is not adhered to. We propose an algorithm based on current cervical cancer screening guidelines to aid providers in identifying whether exit criteria have been met. Until adequate screening has been confirmed, cervical cancer screening should continue.

Introduction

The incidence of cervical cancer (CC) has been markedly reduced because of screening. In the United States and Canada, widespread screening efforts have decreased the incidence from 13.9/100,000 in 1975 to 6.39/100,000 in 2019 in the United States,^[1] and from 14.86/100,000 in 1975 to 7.7/100,000 in 2004 in Canada.^[2] Vaccination against human papillomavirus (HPV) is expected to result in further decreases.^[3] The protection provided by screening, however, has not extended to all. Disparities in CC incidence and outcomes in North America have led to overall suboptimal outcomes, particularly on the basis of age, race, socioeconomic status, and regional differences.^[4,5] Specifically, persons older than 50 years are an inadequately screened group that has experienced preventable CC. CC screening guidelines continue to evolve, with the aim of decreasing the incidence and mortality rates while avoiding excessive testing and intervention.^[6] Persons identified to be at increased risk on the basis of screening or comorbid conditions are recommended to have more frequent testing, with the goal of identifying and treating high-grade preinvasive cervical lesions (severe cervical intraepithelial neoplasia [CIN] 2–3) to prevent cancer.^[6]

This review summarizes CC screening considerations for postmenopausal persons, who are an important population at risk, along with prevention strategies and potential interventions to improve care. At the milestone age of 65 years in the United States and up to 70 years in some parts of Canada,^[7] current guidelines call for CC screening to end if certain criteria are met. Understanding the background and implementation of these criteria is an important focus of this review.

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Table 1. Key CC statistics
Statistic	Value
Age of peak incidence of CC (incidence)⁹
All women	40–44 y (15.6/100,000)
All women with a cervix	65–69 y (27.4/100,000)
White women	40–44 y (15.8/100,000)
White women with a cervix	65–69 y (24.7/100,000)
Black women	≥85 y (29.4/100,000)
Black women with a cervix	65–69 y (53.0/100,000)
Incidence of advanced CC in patients by race¹⁰
White	0.92/100,000
Black	1.55/100,000
Patients lacking appropriate screening at CC diagnosis,^11,12	30%-67.2%
Persons exiting CC screening without meeting criteria¹³	56.7%-64.7%
Rates of inadequate screening by CC stage at diagnosis¹⁴
Regional	70.1%
Distant	68.5%
Localized	31.0%
High-risk HPV prevalence after menopause¹⁵	11.5%
Redetection rate of HPV over 2 y in abstinent midlife women¹⁶	12.0%
Duration of surveillance after CIN2+¹⁷	25 y

CC, cervical cancer; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.

Table 2. 2019 ASCCP risk-based management strata for persons 30 years or older
Risk of CIN3+	Management recommendation^a
5-y risk <0.15%	HPV-based testing in 5 y per screening guidelines
5-y risk 0.15% to <0.55%	HPV-based testing in 3 y
5-y risk 0.55% to <4% immediate risk	HPV-based testing in 1 y
4% to <25% immediate risk	Colposcopy
25% to <60% immediate risk	Treatment or colposcopy
≥60% immediate risk	Expedited treatment

ASCCP, American Society for Colposcopy and Cervical Pathology; CIN3+, cervical intraepithelial neoplasia grade 3 or higher; HPV, human papillomavirus.
^aHPV-based testing options include primary HPV testing with reflex cytologic testing or cotesting with HPV and cytologic testing.
Data from Perkins et al¹⁷ and Cheung et al.⁵¹

Table 3. American Cancer Society recommendations for cervical cancer screening, 2020
The recommendations apply to all asymptomatic individuals with a cervix, regardless of their sexual history or HPV vaccination status, including those who have undergone supracervical hysterectomy and transgender men who retain their cervix. These recommendations represent guidance from the ACS for persons who are initiating cervical cancer screening or have had all normal cervical cancer screening results in the past, or have been returned to routine cervical cancer screening based on follow-up recommendations from the Risk-Based Management Consensus Guidelines. The recommendations do not apply to individuals at increased risk for cervical cancer due to solid-organ or stem cell transplantation, HIV infection or immunosuppression from other causes, or in utero exposure to diethylstilbestrol.
Recommendations
The ACS recommends that individuals with a cervix initiate cervical cancer screening at age 25 y and undergo primary HPV testing every 5 y through age 65 y (preferred). If primary HPV testing is not available, individuals aged 25–65 y should be screened with cotesting (HPV testing in combination with cytology) every 5 y or cytology alone every 3 y (acceptable; strong recommendation).^a
Cotesting or cytology testing alone are included as acceptable options for cervical cancer screening because access to primary HPV testing with a test approved by the FDA for primary screening may be limited in some settings. As the United States makes the transition to primary HPV testing, the use of cotesting or cytology alone for cervical cancer screening will be eliminated from future guidelines.
The ACS recommends that individuals with a cervix who are older than age 65 y, who have no history of cervical intraepithelial neoplasia grade 2 or a more severe diagnosis within the past 25 y, and who have documented adequate negative prior screening in the 10-y period before age 65 y discontinue cervical cancer screening with any modality (qualified recommendation).^a,b
• Adequate negative prior screening is currently defined as 2 consecutive negative HPV tests, or 2 consecutive negative cotests, or 3 consecutive negative cytology tests within the past 10 y, with the most recent test occurring within the recommended interval for the test used. These criteria do not apply to individuals who are currently under surveillance for abnormal screening results.
• Individuals older than age 65 y without conditions limiting life expectancy for whom sufficient documentation of prior screening is not available should be screened until criteria for screening cessation are met.
• Cervical cancer screening may be discontinued in individuals of any age with limited life expectancy.

ACS, American Cancer Society; FDA, US Food and Drug Administration; HPV, human papillomavirus.
^aA strong recommendation conveys the consensus that the benefits of adherence to that intervention outweigh the undesirable effects that may result from screening. Qualified recommendations indicate that there is clear evidence of benefit of screening but less certainty about the balance of benefits and harms or about patients' values and preferences, which could lead to different decisions about screening.
^bOlder than age 65 years means that cervical cancer screening is not recommended for individuals 66 years and older.
From Fontham et al.⁶; used with permission.

Table 4. Canadian Task Force on Preventive Health Care summary of recommendations for cervical cancer screening
Recommendations are presented for the use of cervical cytology (Pap tests) for women with no symptoms of cervical cancer who are or have been sexually active, regardless of sexual orientation. The recommendations do not apply to women with symptoms of cervical cancer (eg, abnormal vaginal bleeding), women with previous abnormal results on screening (unless they have been cleared to return to normal screening), women who do not have a cervix (because of hysterectomy), women who are immunosuppressed (eg, as a result of organ transplantation, chemotherapy, chronic corticosteroid treatment, HIV infection) or women who have limited life expectancy such that they would not benefit from screening.
The recommendations do not address screening with HPV testing (alone or in combination with Pap testing). In our judgment, such a recommendation would be premature until the evidence in this area is further developed.
Cytology (conventional or liquid-based, manual or computer-assisted)
• For women younger than 20 y, we recommend not routinely screening for cervical cancer. (Strong recommendation; high-quality evidence)
• For women aged 20–24 y, we recommend not routinely screening for cervical cancer. (Weak recommendation; moderate-quality evidence)
• For women aged 25–29 y, we recommend routine screening for cervical cancer every 3 y. (Weak recommendation; moderate quality evidence)
• For women aged 30–69 y, we recommend routine screening for cervical cancer every 3 y. (Strong recommendation; high-quality evidence)
• For women 70 y or older who have undergone adequate screening (ie, 3 successive negative Pap test results in the last 10 y), we recommend that routine screening may stop. For all other women 70 years or older, we recommend continued screening until 3 negative test results have been obtained. (Weak recommendation; low-quality evidence)