From the Editor

Why do so many women aged 65 years and older die of cervical cancer?

OBG Manag. 2019 August;31(8):7-10

References

Hammer A, Kahlert J, Gravitt PE, et al. Hysterectomy-corrected cervical cancer mortality rates in Denmark during 2002-2015: a registry-based cohort study. Acta Obstet Gynecol Scand. 2019;98:1063-1069.
Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;123:1044-1050.
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. Practice Bulletin No. 168: cervical cancer screening and prevention. Obstet Gynecol. 2016;128:e111-30.
Curry SJ, Krist AH, Owens DK, et al; US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:674-686.
Stang A, Hawk H, Knowlton R, et al. Hysterectomy-corrected incidence rates of cervical and uterine cancers in Massachusetts, 1995-2010. Ann Epidemiol. 2014;24:849-854.
Hallowell BD, Endeshaw M, McKenna MT, et al. Cervical cancer death rates among U.S.- and foreign-born women: U.S., 2005-2014. Am J Prev Med. 2019;56:869-874.
Lindström AK, Hermansson RS, Gustavsson I, et al. Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing. PLoS One. 2018;13:e0207714.
Kjaer SK, Munk C, Junge J, et al. Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ACSUC/LSIL, HSIL, or cervical cancer: what is the potential for prevention? Cancer Causes Control. 2014;25:179-189.
Andersen B, Christensen BS, Christensen J, et al. HPV-prevalence in elderly women in Denmark. Gynecol Oncol. 2019;154:118-123.
Gravitt PE, Winer RL. Natural history of HPV infection across the lifespan: role of viral latency. Viruses. 2017;9:E267.
Hinten F, Hilbrands LB, Meeuwis KAP, et al. Reactivation of latent HPV infections after renal transplantation. Am J Transplant. 2017;17:1563-1573.
Leonard SM, Pereira M, Roberts S, et al. Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women. Sci Rep. 2016;6:20847.
Cervical cancer screening. Cancer Council website. https://www.cancer.org.au/about-cancer/early-detection/screening-programs/cervical-cancer-screening.html. Updated March 15, 2019. Accessed July 23, 2019.

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...