By Alexandra Samborski, MD
Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY
SYNOPSIS: Women diagnosed with cervical cancer after age 65 years are more likely to have locally advanced or metastatic disease, and survival decreases with increasing age and stage of diagnosis.
SOURCE: Lichter KE, et al. Understanding cervical cancer after the age of routine screening: Characteristics of cases, treatment, and survival in the United States. Gynecol Oncol 2022;165:67-74.
More than 14,000 women in the United States are expected to be diagnosed with cervical cancer in 2022, with 20% of these being patients older than 65 years of age.1 Current screening guidelines by the United States Preventive Services Task Force (USPSTF) and American Cancer Society (ACS) recommend discontinuation of routine cervical cancer screening at age 65 years.2-4 As a result of population growth and increased life expectancy, the number of women older than age 65 years is expected to increase, and it will take decades before the effect of human papillomavirus (HPV) vaccination on cervical cancer rates is seen in this age group. This study aimed to describe the characteristics, treatment, and survival of women older than age 65 years diagnosed with cervical cancer.
This is a retrospective study that used the Surveillance, Epidemiology, and End Results (SEER)-linked Medicare dataset. This linked dataset incorporates the SEER program’s population-based tumor registry for 11 geographical areas and the Medicare claims data for the health services these patients accessed. Women were included if they were > 65 years of age, were diagnosed with cervical cancer between Jan. 1, 2004, and Dec. 31, 2013, and were accounted for in both datasets. Information was obtained on patients’ demographics, tumor characteristics, stage of disease, and treatments received. The Klabunde-modified Charlson comorbidity index scale was used to calculate the comorbidity score. Descriptive statistics were used. Factors associated with the receipt of treatment and risk of death within five years were evaluated with Poisson and Cox regression models. Both univariate and multivariate analyses were completed. The Kaplan-Meier method was used to estimate cancer-specific survival. A total of 2,274 women were identified who met the inclusion criteria, with a median age of 76.1 years at the time of cervical cancer diagnosis. Sixty-four percent of patients were non-Hispanic white, 54% had a comorbidity index ≥ 1, 66% were diagnosed with a squamous cell carcinoma, and 18% were diagnosed with an adenocarcinoma. Nearly 63% of patients were diagnosed with stage 2 or higher cervical cancer, including 23% diagnosed at stage 4. Eighty-five percent of patients received treatment, most commonly surgery followed by chemotherapy and/or radiotherapy. The patients with the lowest treatment rates were those > 80 years of age, those with comorbidity scores ≥ 3, those with stage 4 disease, and those with non-squamous cell and non-adenocarcinoma histology.
Survival data also were calculated, with the median survival time following diagnosis being 56 months. The five-year cancer-specific survival was 49.5%, with this decreasing significantly with increasing age group (P < 0.01) and with increasing stage at diagnosis (P < 0.01). Black women also had significantly lower five-year survival than all other races/ethnicities (44.6% five-year survival; P = 0.01), although this no longer was significant after multivariable adjustment. Patients with non-squamous cell carcinoma and non-adenocarcinoma also had lower five-year survival rates at 35.4% (P < 0.01). All forms of treatment, other than chemotherapy alone, were associated with higher cancer-specific survival than no treatment.
COMMENTARY
Current recommendations are to discontinue routine cervical cancer screening after age 65 years for patients who have been screened adequately and have not had a lesion CIN2 or greater in the prior 25 years. A statement from the ACS defines adequate screening as “two consecutive, negative primary HPV tests, or two negative cotests, or three negative cytology tests within the past 10 years, with the most recent test occurring within the past three to five years, depending on the test used.”3 These screening recommendations are intended to balance the benefits of early disease detection or prevention and the risk of unnecessary colposcopies in the setting of patients’ anticipated life expectancy.
Despite these recommendations for when it is acceptable to discontinue screening, there is a high percentage of cervical cancer patients who receive their diagnosis after this age. This study shows that patients diagnosed with cervical cancer after age 65 years are less likely to be diagnosed with early stage disease, and treatment and survival rates decrease with increasing age. The data presented here prompt the question: Should we continue routine cervical cancer screening past age 65 years?
In this study, investigators did not differentiate which patients previously had received adequate screening and exited the screening protocol and which had not received adequate screening. In clinical practice, it can be challenging to determine if patients have, in fact, been screened adequately because of patients’ inability to accurately remember their Pap history and the disconnected medical records that hold their results. Understanding the likelihood of developing cervical cancer, even with adequate screening according to current guidelines, is a key piece of information needed to make this determination. A prior study showed that 18% of women > 60 years of age with cervical cancer had been screened adequately and were eligible to discontinue screening. Of those diagnosed with advanced-stage disease, there was not a statistically significant difference between those who received adequate screening and those who did not.5 Given the fact that it can take 10 years for a cervical cancer to develop, and nearly one-third of the patients in this study were > 80 years of age, one could infer that many of these patients would not have had a pre-cancerous lesion noted at age 65 years and, thus, extended screening would be necessary to identify these cases at an early stage.
Interpreting cytology results in the post-menopausal group can be more challenging, given the hypoestrogenic state and its effect on the cervix. The transformation zone generally is within the endocervical canal at this age, making adequate sampling of this area difficult.6 Additionally, there are higher rates of false-positive cytology results caused by the atrophy of the cervix. Given this fact, using HPV-based screening in this age group may be more appropriate.7 As the population of women older than 65 years of age is expected to increase and the number of total hysterectomies is expected to decrease, the number of cervical cancer diagnoses in this age group likely will rise.8 Additionally, this is a population not currently vaccinated for HPV. Over time, as the population that has received the HPV vaccine ages, this will change and, one hopes, rates of cervical cancer will decrease.
While the current guidelines remain, these data support having a discussion with patients regarding the pros and cons of continued cervical cancer screening to allow for shared decision-making regarding when is the optimal time for each patient to stop. It also is important to keep cervical dysplasia or malignancy on the differential for older patients presenting with vaginal bleeding, vaginal discharge, or a lesion identified with physical exam. Just as the screening guidelines have changed in the past based on the most current evidence and understanding of the disease, we can anticipate them to evolve as we learn more, and perhaps someday screening after the age of 65 years will be incorporated.
REFERENCES
- National Cancer Institute. Cancer Stat Facts: Cervical cancer. https://seer.cancer.gov/statfacts/html/cervix.html
- Perkins RB, et al. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2020;24:102-131.
- Fontham ETH, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin 2020;70:321-346.
- US Preventive Services Task Force, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;320:674-686.
- Hammer A, et al. Cervical cancer screening history prior to a diagnosis of cervical cancer in Danish women aged 60 years and older - A national cohort study. Cancer Med 2019;8:418-427.
- Gilani SM, et al. Cytohistologic correlation in premenopausal and postmenopausal women. Acta Cytol 2013;57:575-580.
- Kiff JM, et al. Cervical cancer screening in postmenopausal women: Is it time to move toward primary high-risk human papillomavirus screening? J Womens Health (Larchmt) 2021;30:972-978.
- Dilley S, et al. It’s time to re-evaluate cervical cancer screening after age 65. Gynecol Oncol 2021;162:200-202.
Women diagnosed with cervical cancer after age 65 years are more likely to have locally advanced or metastatic disease, and survival decreases with increasing age and stage of diagnosis.
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