Angela A. Cleveland

Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008–2015

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population‐based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high‐risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9‐valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21–24 year age group (annual percent change [APC] overall: −22.1%, 95% CI: −33.9 to −8.2; APC among screened: −16.1%, 95% CI: −28.8 to −1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.

HPV type‐specific trends in cervical precancers in the United States, 2008 to 2016

AbstractDeclines in cervical intraepithelial neoplasia grades 2 to 3 and adenocarcinoma in situ (CIN2+) observed among young women suggest impact from human papillomavirus (HPV) vaccination. To further evaluate vaccine impact including cross‐protection and type replacement, we described high‐risk (HR)‐HPV type‐specific cervical precancer incidence rates among women aged 20 to 39 years, 2008 to 2016. We analyzed cross‐sectional population‐based data on 18 344 cases of CIN2+ from a 5‐site surveillance system. Diagnostic specimens were tested for individual HPV types, including 14 HR‐HPV types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68). We estimated age‐specific annual HR‐HPV type‐specific CIN2+ incidence per 100 000 screened women for individual types, vaccine HR‐HPV types (HPV16/18) and nonvaccine HR‐HPV types (non‐HPV16/18). We evaluated trends using average annual percent changes (AAPC) and 95% confidence intervals (CI), and estimated total declines by comparing 2015‐2016 to 2008‐2009 using incidence rate ratios. Among 20‐24‐year‐olds, HPV16/18‐CIN2+ declined from 2008 through 2016 (AAPC: −21.3%, 95% CI: −28.1%, −13.8%), whereas no trend was observed for non‐HPV16/18‐CIN2+ (AAPC: −1.8%, 95% CI: −8.1%, 4.9%). After 2010, CIN2+ among 20‐24‐year‐olds was more often caused by nonvaccine vs vaccine HR‐HPV types. No significant declining trends were observed in older age groups. In 2015‐2016 compared with 2008‐2009, HPV16‐CIN2+ declined 78%, HPV18‐CIN2+ 72% and HPV31‐CIN2+ 51% among 20‐24‐year‐olds; no increases were observed in type‐specific CIN2+ incidence. Among 25‐29‐year‐olds, HPV16‐CIN2+ declined 18%; CIN2+ attributed to seven nonvaccine types increased significantly. No significant declines were observed in older groups. Significant declines in HPV16/18‐CIN2+ in 20‐24‐year‐olds and HPV16‐CIN2+ in 25‐29‐year‐olds corroborate impact of HPV vaccination. A declining trend in HPV31‐CIN2+ is consistent with cross‐protection from vaccination.