Cervical cancer screening guidelines have changed significantly in the last 5 years and new approaches to screening are emerging, due to our understanding of the natural history of HPV and it’s role in the development of high-grade lesions and cervical cancer.  Additionally, improved screening is possible because of the availability of highly sensitive HPV tests.

Cervical cancer is preventable and is caused by oncogenic or high-risk types of Human Papillomavirus (HPV).  The majority of women will be infected by HPV at some point, but most will clear the infection by 24 months.  The peak age of having HPV is the mid twenties and by the age of 50, 80% of women will have been infected.  Long-term persistent infection is necessary for the development of neoplasia and progression to invasive cancer.  The advent of cervical cancer screening more than 60 years ago by the Papanicolaou smear has decreased cervical cancer by 75% in the United States, but there continues to be more than 12,000 cases of cervical cancer diagnosed every year.

The greatest impact in cervical cancer prevention would be by screening under screened and unscreened women. Additionally, the 9-valent HPV vaccine which can reduce cervical cancer rates by 90% and shows long term efficacy has been underutilized.  Primary prevention with the vaccine is approved for both young men and women and the vaccine provides immunogenicity for 9 types including HPV 16 and 18 which cause 70% of cervical cancer and additionally, HPV 16 causes 90% of anal cancer which is on the rise.  HPV 16 is also seen as a causative agent in non-genital cancers of the head and neck.

The 2012 cervical cancer screening guidelines by the American Society for Colposcopy and Cervical Pathology (ASCCP), the American Cancer Society (ACS) and the American Society for Clinical Pathology (ASCP) were developed to increase benefit and decrease harm to women.  The guidelines made major changes in screening with delay of the first Pap to age 21, widened screening intervals to every 3 years by Pap alone and with the addition of co-testing women at 30 and older with Pap and HPV testing every 5 years.  The guidelines recommend exiting women out of cervical screening at age 65 when there has been adequate negative screening in the previous 10 years with 3 negative Pap tests or 2 rounds of negative Pap and HPV and no abnormal tests.  The addition of HPV testing in screening women allows for the identification of women who may have disease that was missed by the Pap and identifies women with future risk.  Women who are HPV positive need to be followed diligently as long as the virus is present in the cells.  The HPV test is highly sensitive though the Pap has a greater level of specificity.

The newest strategy for cervical cancer prevention by screening, is primary “stand alone” HPV testing every 3 years, which has been FDA approved for women 25 and older.  The Athena trial that led to the approval of primary HPV testing showed that 30% of the high-grade disease in the study population occurred in the 25 to 29 year old age group.  For that reason, the FDA approved primary screening starting at age 25.  The guideline for co-testing remains starting at 30 and older and was based on data at the time.  The cobas test is the only HPV test out of the 4 currently FDA approved HPV tests on the market, that has been approved for primary screening.  On every sample, the cobas test provides a positive or negative result for genotypes 16 and 18 and for a panel of 12 other high-risk HPV types.  Finding those women with the presence of HPV genotypes 16 or 18 allows for the identification of the subset of women with significant risk for the development of neoplastic change and for possible progression to invasive cancer.  In the published clinical guidance for HPV primary screening, women who test negative for HPV receive routine screening with a repeat HPV test in 3 years and this is due to the high negative predictive value of the HPV test.  Women who test positive for HPV 16 or 18 are referred for immediate colposcopic evaluation and women who are negative for HPV 16 and 18, but have a positive test of the panel of 12 other high risk types receive a reflex Pap test and any abnormal Pap leads to immediate colposcopic examination.  Those women with a negative reflex Pap and a positive test for the panel of 12 other types receives a follow-up HPV test in 12 months.

The changes in cervical screening with a later age of initiation of screening, widened screening intervals, co-testing with Pap and HPV and primary HPV screening mean that education of clinicians and patients has never been more important.  It is critical to use Pap and HPV testing appropriately and to screen those women who have not had adequate screening.

See Nancy Berman, MSN, ANP-BC, NCMP, FAANP speak in 2018 at a Skin, Bones, Hearts & Private Parts CME/CE Conference for PAs, NPs, MDs, and DOs.