In the Journals

CIN2/3 from HPV infection linked to long-term risk for anal, vaginal, vulvar cancers

Women with a history of cervical intraepithelial neoplasia 2 or 3 arising from HPV infection appeared to have an increased risk for developing anal, vaginal and vulvar cancers, according to the results of a national cohort study.

Further, those risks persisted long term, often beyond 20 years.

Susanne Kjaer

Susanne Krüger Kjær

“The HPV vaccine is prophylactic, and if we can prevent HPV infection from occurring in the first place, we can prevent some of these conditions that result from persistent infection,” Susanne Krüger Kjær, MD, professor of gynecological cancer epidemiology at the Danish Cancer Society Research Center at Juliane Marie Centre of Copenhagen University Hospital in Copenhagen, Denmark, said in a press release.

Previous evidence has shown cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3) — which develops due to high-risk HPV infection — increases risk for noncervical anogenital cancers; however, data on long-term risks for anal, vaginal and vulvar cancers had been lacking.

Kjær and colleagues evaluated data from more than 2.7 million women who were born between 1918 and 1990, and who lived in Denmark between 1978 and 2012. Researchers followed women until 2012, they emigrated, or they developed rectal or anogenital cancer.

The majority of women did not have history of CIN2/3 (n = 2,769,801), whereas 52,135 had a history of CIN2 and 104,155 had a history of CIN3.

Anal, vulvar and vaginal cancers developed in 66 women with a history of CIN2 and 293 women with a history of CIN3.

Results of an age-adjusted analysis showed women with a history of CIN2 had an increased risk for anal cancer (HR = 2.9; 95% CI, 2-4.1), vulvar cancer (HR = 2.5; 95% CI, 1.6-3.8) and vaginal cancer (HR = 8.1; 95% CI, 5.5-15). These risks were even greater in women with a history of CIN3 for anal cancer (HR = 4.2; 95% CI, 3.4-5), vulvar cancer (HR = 4; 95% CI, 3.2-4.9) and vaginal cancer (HR = 17.1; 95% CI, 12.8-22.9).

Neither cohort had an increased risk for rectal cancer.

Although the risks were highest the first year following CIN2/3 diagnosis, they appeared to persist long term.

Twenty-five years or more following CIN3 diagnosis, the HRs for risk were 4.8 (95% CI, 3.3-7) for anal cancer, 5.5 (95% CI, 2.4-12.3) for vaginal cancer and 3.2 (95% CI, 2-5.3) for vulvar cancer.

Women with a history of CIN2 also experienced prolonged risk, although to a lesser degree.

Twenty years or more following CIN2 diagnosis, the HR was 3.5 (95% CI, 2-5.9) for anal cancer and 2.6 (95% CI, 1.3-5.2) for vulvar cancer. Ten or more years following CIN2 diagnosis, the HR was 5 (95% CI, 2.2-11.2) for vaginal cancer.

“We had thought that perhaps the women with CIN3 were the ones who were being treated by doctors and, therefore, receiving more examination and consequently getting diagnosed with other cancers,” Kjær said in a press release. “But the risks persist for many years and, therefore, our findings cannot be explained by surveillance bias.”

Researchers acknowledged that due to incomplete registration data, older women in the study may have had a CIN2/3 diagnosis that was not registered. Also, researchers did not have information on the HPV type in CIN2/3, and thus were unable to determine that HPV was the causal factor of subsequent cancers.

“High-risk HPV infection is an essential factor for the development of both CIN and certain anogenital cancers, and the presence of high-grade CIN is a good proxy for persistent high-risk HPV infection,” Kjær and colleagues wrote. by Nick Andrews

Disclos ure: Kjær reports speaker and advisory board fees and unrestricted research grants from Merck and Sanofi Pasteur MSD. One other researcher reports travel accommodations from Sanofi Pasteur MSD.

Women with a history of cervical intraepithelial neoplasia 2 or 3 arising from HPV infection appeared to have an increased risk for developing anal, vaginal and vulvar cancers, according to the results of a national cohort study.

Further, those risks persisted long term, often beyond 20 years.

Susanne Kjaer

Susanne Krüger Kjær

“The HPV vaccine is prophylactic, and if we can prevent HPV infection from occurring in the first place, we can prevent some of these conditions that result from persistent infection,” Susanne Krüger Kjær, MD, professor of gynecological cancer epidemiology at the Danish Cancer Society Research Center at Juliane Marie Centre of Copenhagen University Hospital in Copenhagen, Denmark, said in a press release.

Previous evidence has shown cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3) — which develops due to high-risk HPV infection — increases risk for noncervical anogenital cancers; however, data on long-term risks for anal, vaginal and vulvar cancers had been lacking.

Kjær and colleagues evaluated data from more than 2.7 million women who were born between 1918 and 1990, and who lived in Denmark between 1978 and 2012. Researchers followed women until 2012, they emigrated, or they developed rectal or anogenital cancer.

The majority of women did not have history of CIN2/3 (n = 2,769,801), whereas 52,135 had a history of CIN2 and 104,155 had a history of CIN3.

Anal, vulvar and vaginal cancers developed in 66 women with a history of CIN2 and 293 women with a history of CIN3.

Results of an age-adjusted analysis showed women with a history of CIN2 had an increased risk for anal cancer (HR = 2.9; 95% CI, 2-4.1), vulvar cancer (HR = 2.5; 95% CI, 1.6-3.8) and vaginal cancer (HR = 8.1; 95% CI, 5.5-15). These risks were even greater in women with a history of CIN3 for anal cancer (HR = 4.2; 95% CI, 3.4-5), vulvar cancer (HR = 4; 95% CI, 3.2-4.9) and vaginal cancer (HR = 17.1; 95% CI, 12.8-22.9).

Neither cohort had an increased risk for rectal cancer.

Although the risks were highest the first year following CIN2/3 diagnosis, they appeared to persist long term.

Twenty-five years or more following CIN3 diagnosis, the HRs for risk were 4.8 (95% CI, 3.3-7) for anal cancer, 5.5 (95% CI, 2.4-12.3) for vaginal cancer and 3.2 (95% CI, 2-5.3) for vulvar cancer.

Women with a history of CIN2 also experienced prolonged risk, although to a lesser degree.

Twenty years or more following CIN2 diagnosis, the HR was 3.5 (95% CI, 2-5.9) for anal cancer and 2.6 (95% CI, 1.3-5.2) for vulvar cancer. Ten or more years following CIN2 diagnosis, the HR was 5 (95% CI, 2.2-11.2) for vaginal cancer.

“We had thought that perhaps the women with CIN3 were the ones who were being treated by doctors and, therefore, receiving more examination and consequently getting diagnosed with other cancers,” Kjær said in a press release. “But the risks persist for many years and, therefore, our findings cannot be explained by surveillance bias.”

Researchers acknowledged that due to incomplete registration data, older women in the study may have had a CIN2/3 diagnosis that was not registered. Also, researchers did not have information on the HPV type in CIN2/3, and thus were unable to determine that HPV was the causal factor of subsequent cancers.

“High-risk HPV infection is an essential factor for the development of both CIN and certain anogenital cancers, and the presence of high-grade CIN is a good proxy for persistent high-risk HPV infection,” Kjær and colleagues wrote. by Nick Andrews

Disclos ure: Kjær reports speaker and advisory board fees and unrestricted research grants from Merck and Sanofi Pasteur MSD. One other researcher reports travel accommodations from Sanofi Pasteur MSD.