Cotesting Best for Cervical Cancer Screening, But Cytology Doesn’t ID Other Gynecological Cancers

Despite the fact that the Pap smear has been around for 70-plus years and is credited with greatly reducing the incidence of cervical cancer, screening remains imperfectly executed in the United States. Adherence to guidelines is suboptimal and plagued nationally by a combination of overscreening, underscreening, and poor management of women with abnormal test results. Lack of guideline adherence is in part driven by confusion regarding the use of conventional cytology testing versus newer cotesting strategies (Pap cytology plus human papillomavirus [HPV] DNA testing).

Two abstracts presented at the Society of Gynecologic Oncology’s (SGO’s) Annual Meeting on Women’s Cancer (March 19-22; San Diego) address economic and clinical benefit considerations of cervical cytology screening.

In a population partially vaccinated against HPV, a cotesting strategy has the highest screening costs, but also the lowest cervical cancer incidence and mortality, according to an abstract presented at SGO by Catherine Popadiuk, M.D., from of Memorial University of Newfoundland in Canada.

Popadiuk and colleagues used the Cancer Risk Management Model-Human Papillomavirus (CRMM-HPV) Canadian population microsimulation model to assess three screening strategies in a vaccinated population (HPV types 6/11/16/18). The three strategies included: triennial Pap smear in 25 to 69 year olds (PAP3); triennial Pap smear in 25 to 29 year olds with HPV DNA testing every five years from ages 30 to 69 years (PAP3/HPV5), and triennial Pap smear in 25 to 29 year olds and Pap/HPV cotesting every 5 years from ages 30 to 69 years (cotest). The model assumed that the vaccination rate was 70 percent for girls aged 12 years when the program started in 2007 and that there was a 70 percent participation rate for screening in eligible women beginning in 2015.

The researchers found that cotesting cut cervical cancer incidence and mortality per 100,000 by 5.8 percent on average, compared with the Pap smear between 2015 and 2050. Over a lifetime, PAP3/HPV5 and cotesting resulted in 2.3 percent and 7.5 percent fewer cases than PAP3, respectively, plus 2.9 percent and 7.9 percent fewer deaths compared with Pap3, respectively. Cotesting was projected to require the most annual colposcopies (n=201,800 versus 148,900 and 102,600 for Pap3 and Pap3/HPV5 strategies, respectively). When considering lifetime costs of vaccination, cervical screening, and treatment, cotesting was the most costly ($27.98 billion), while PAP3/HPV5 was the least costly ($20.48 billion). Considering just direct screening costs, cotesting remained the most expensive strategy ($23.22 billion).

While the benefits of screening to cut the incidence of cervical cancer are undeniable, regardless of screening strategy, researchers presented findings suggesting that cervical cancer screening is unwarranted for detecting endometrial or ovarian cancers, according to a featured poster presented by Alexandra Freeman, M.D., from Kaiser Permanente San Francisco Medical Center, San Francisco.

The Kaiser Permanente researchers identified 1,545,126 women who underwent cervical cytology screening in the health care system from 2009 through 2014. Abnormal cervical cytology was defined as: atypical glandular cells, other (normal postmenopausal endometrial cells), or malignant. Endometrial and ovarian cancer cases were confirmed using a local cancer registry over the study period. Laboratory databases, including reasons for the visit based on the history provided with the Pap requisition, were reviewed to determine any symptoms of endometrial or ovarian cancer.

The researchers found that over the five years 0.3 percent of women had abnormal glandular cell cytology results. Over the same period there were 3,898 primary invasive endometrial cancers and 1,434 primary invasive ovarian cancers. Among women diagnosed with endometrial and ovarian cancer, 5.0 percent and 0.9 percent, respectively, had abnormal cervical cytology in the 12 months prior to their cancer diagnosis. Visit notes indicate that 58.7 percent and 61.5 percent of those with abnormal cytology were symptomatic for endometrial and ovarian cancers, respectively at the time of screening.

“Failure to diagnose otherwise unsuspected endometrial or ovarian cancer has been described as one potential reason to avoid replacing cotesting with primary HPV screening,” the authors write. “Performance of cervical cytology on 1.5 million women for the purpose of detecting the number of occult endometrial or ovarian cancers described above does not seem warranted.”

Takeaway: Cotesting (cervical cytology screening plus HPV DNA testing) remains costly, but is the most effective strategy for cutting the number of cases and deaths from cervical cancer. However, questions remain about the utility of cytology for diagnosing other gynecological cancers.