In the Journals

Incidence of high-grade cervical lesions has declined due to screening, vaccination

The incidence of high-grade cervical lesions has decreased in young women in the U.S. since the approval of HPV vaccines, according to study results.

However, this reduction may also be a reflection of changes to cervical cancer screening recommendations, researchers said. In the previous decade, the recommended age to commence cervical cancer screening was increased to 21 years and screening intervals have lengthened.

Asymptomatic high-grade cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (CIN2+) lesions can progress into invasive cervical cancer if left untreated, according to study background. Incidence of these lesions can also be monitored as early indicators of HPV vaccination impact.

Susan Hariri, PhD, MPH, an epidemiologist in the department of STD prevention at the CDC, and colleagues accessed data from the HPV-IMPACT Project — a population-based laboratory surveillance system designed to monitor the impact of HPV vaccination — to observe CIN2+ detection rates among women aged 18 to 39 years since the introduction of the HPV vaccine.

The HPV-IMPACT Project collected data from catchments areas in eight contiguous cities in California, Connecticut, New York and Oregon, each with a population of 230,000 to 330,000 women aged 18 years or older.

The researchers calculated age-stratified CIN2+ incidence rates for each catchment area and used administrative and survey data to estimate annual cervical screenings in California, New York and Oregon.

The analysis included data from 9,119 women with CIN2+ lesions reported between 2008 and 2012.

During this period, CIN2+ incidence significantly decreased among women aged 18 to 20 years in all four states. The incidence per 100,000 women decreased in California from 94 to 5, in Connecticut from 450 to 57, in New York from 299 to 43, and in Oregon from 202 to 37 (P < .0001 for all).

Further, CIN2+ incidence significantly declined among women aged 21 to 29 in Connecticut (from 762 to 589 per 100,000 women) and New York (from 770 to 465 per 100,000 women; P < .001 for both).

No decline in incidence occurred among women aged 30 to 39 years.

However, screening rates also declined during this period, with the most pronounced decreases occurring among women aged 18 to 20 years (Oregon, 67%; New York, 80%; California, 88%). Although the percentage of women screened during the first year of study varied by state, rates dropped to less than 10% in all areas by 2012, with the sharpest decline observed between 2009 and 2010.

However, the reduction in CIN2+ rate exceeded estimated screening declines in all states (California, 7%; New York, 5%; Oregon, 15%).

Screening rates also decreased among women aged 21 to 29 years although to a lesser degree (Oregon, 13%; New York, 26%; California, 27%). A larger, corresponding decline (40%) in CIN2+ incidence occurred only in New York.

Among women aged 30 to 39 years, screening decreases occurred in all catchment areas (California, 3%; New York, 18%; Oregon, 21%); however, CIN2+ incidence remained unchanged.

“To our knowledge, this is the first examination of trends in CIN2+ diagnosis in multiple populations of U.S. women in the new era of cervical cancer prevention,” Hariri and colleagues concluded. “Importantly, our data illustrate the challenges in assessing HPV vaccine impact on cervical precancers in the U.S. and emphasize the importance of additional information such as types of HPV detected in these lesions to assist in this determination.”

Although study data accounted for multiple potentially confounding factors leading to decreases in cervical lesion incidence, the researchers also provide important information for future study of postvaccination cervical cancer incidence, Harinder Brar, MD, and Allan Covens, MD, both of the division of gynecological oncology at University of Toronto, wrote in an accompanying editorial.

“Despite the confounding effect of changing cervical cancer screening guidelines, the findings cannot be completely ignored,” Brar and Covens wrote. “[Hariri et al] also highlight a significant confounder that future studies need to address. With wider acceptance and standardization of cervical cancer screening guidelines and with an increasing number of women entering the vaccinated cohort, the magnitude of vaccine effectiveness should become more obvious. Further studies are needed to assess the changes in high-grade histological abnormalities in the postvaccine era. More importantly, these histological changes need to be correlated with patient-level vaccination status and population-level vaccine uptake rates.” – by Cameron Kelsall

Disclosure: Hariri reports no relevant financial disclosures. One study researcher reports personal fees from Merck. Covens reports honoraria and an educational grant from Merck.

The incidence of high-grade cervical lesions has decreased in young women in the U.S. since the approval of HPV vaccines, according to study results.

However, this reduction may also be a reflection of changes to cervical cancer screening recommendations, researchers said. In the previous decade, the recommended age to commence cervical cancer screening was increased to 21 years and screening intervals have lengthened.

Asymptomatic high-grade cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (CIN2+) lesions can progress into invasive cervical cancer if left untreated, according to study background. Incidence of these lesions can also be monitored as early indicators of HPV vaccination impact.

Susan Hariri, PhD, MPH, an epidemiologist in the department of STD prevention at the CDC, and colleagues accessed data from the HPV-IMPACT Project — a population-based laboratory surveillance system designed to monitor the impact of HPV vaccination — to observe CIN2+ detection rates among women aged 18 to 39 years since the introduction of the HPV vaccine.

The HPV-IMPACT Project collected data from catchments areas in eight contiguous cities in California, Connecticut, New York and Oregon, each with a population of 230,000 to 330,000 women aged 18 years or older.

The researchers calculated age-stratified CIN2+ incidence rates for each catchment area and used administrative and survey data to estimate annual cervical screenings in California, New York and Oregon.

The analysis included data from 9,119 women with CIN2+ lesions reported between 2008 and 2012.

During this period, CIN2+ incidence significantly decreased among women aged 18 to 20 years in all four states. The incidence per 100,000 women decreased in California from 94 to 5, in Connecticut from 450 to 57, in New York from 299 to 43, and in Oregon from 202 to 37 (P < .0001 for all).

Further, CIN2+ incidence significantly declined among women aged 21 to 29 in Connecticut (from 762 to 589 per 100,000 women) and New York (from 770 to 465 per 100,000 women; P < .001 for both).

No decline in incidence occurred among women aged 30 to 39 years.

However, screening rates also declined during this period, with the most pronounced decreases occurring among women aged 18 to 20 years (Oregon, 67%; New York, 80%; California, 88%). Although the percentage of women screened during the first year of study varied by state, rates dropped to less than 10% in all areas by 2012, with the sharpest decline observed between 2009 and 2010.

However, the reduction in CIN2+ rate exceeded estimated screening declines in all states (California, 7%; New York, 5%; Oregon, 15%).

Screening rates also decreased among women aged 21 to 29 years although to a lesser degree (Oregon, 13%; New York, 26%; California, 27%). A larger, corresponding decline (40%) in CIN2+ incidence occurred only in New York.

Among women aged 30 to 39 years, screening decreases occurred in all catchment areas (California, 3%; New York, 18%; Oregon, 21%); however, CIN2+ incidence remained unchanged.

“To our knowledge, this is the first examination of trends in CIN2+ diagnosis in multiple populations of U.S. women in the new era of cervical cancer prevention,” Hariri and colleagues concluded. “Importantly, our data illustrate the challenges in assessing HPV vaccine impact on cervical precancers in the U.S. and emphasize the importance of additional information such as types of HPV detected in these lesions to assist in this determination.”

Although study data accounted for multiple potentially confounding factors leading to decreases in cervical lesion incidence, the researchers also provide important information for future study of postvaccination cervical cancer incidence, Harinder Brar, MD, and Allan Covens, MD, both of the division of gynecological oncology at University of Toronto, wrote in an accompanying editorial.

“Despite the confounding effect of changing cervical cancer screening guidelines, the findings cannot be completely ignored,” Brar and Covens wrote. “[Hariri et al] also highlight a significant confounder that future studies need to address. With wider acceptance and standardization of cervical cancer screening guidelines and with an increasing number of women entering the vaccinated cohort, the magnitude of vaccine effectiveness should become more obvious. Further studies are needed to assess the changes in high-grade histological abnormalities in the postvaccine era. More importantly, these histological changes need to be correlated with patient-level vaccination status and population-level vaccine uptake rates.” – by Cameron Kelsall

Disclosure: Hariri reports no relevant financial disclosures. One study researcher reports personal fees from Merck. Covens reports honoraria and an educational grant from Merck.