In the Journals

High-grade dysplasia increases long-term risk for HPV-related cancers

Women maintained an increased risk for premalignancies and carcinomas of the anus, vulva, vagina and oropharynx 20 years after cervical intraepithelial neoplasia grade 3 diagnosis, according to results of a population-based study.

“Patients should be informed on an individual basis about this increased risk,” Renée M.F. Ebisch, MD, PhD candidate in the department of obstetrics and gynecology at Radboud University Medical Center in The Netherlands, told HemOnc Today.

Previous studies indicated women with cervical intraepithelial neoplasia grade 3 (CIN3) had increased risk for carcinomas of the anogenital and head and neck areas. However, whether these patients had an increased risk for high-grade premalignancies after diagnosis had not been reported.

Researchers individually matched 89,018 women (median age at diagnosis, 35 years) diagnosed with CIN3 between 1990 and 2010 — identified from the Dutch nationwide registry of histopathology and cytopathology — with a control group of 89,018 women (median age, 36 years) without CIN3.

Researchers evaluated all subsequent cases of high-risk HPV-associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015.

Of women with a previous CIN3 diagnosis, 299 had HPV-related carcinomas and 634 had HPV-related premalignancies.

The controls accrued 1,262,998 person-years and reported 48 HPV-related carcinomas and 50 HPV-related premalignancies.

Researchers reported incidence rate ratios (IRR) in women with CIN3 of 6.2 (95% CI, 4.6-8.46) for any HPV-related carcinoma, 12.75 (95% CI, 9.56-17) for any HPV-related premalignancy, and 9.68 (95% CI, 7.77-12.05) for any HPV-related carcinoma or premalignancy.

Women with a history of CIN3 had increased incidence of anal cancer (IRR = 3.85; 95% CI, 2.32-6.37), anal intraepithelial neoplasia grade 3 (IRR = 6.68; 95% CI, 3.64-12.25), vulvar cancer (IRR = 4.97; 95% CI, 3.26-7.57), vulvar intraepithelial neoplasia grade 3 (IRR = 13.66; 95% CI, 9.69-19.25), vaginal cancer (IRR = 86.08, 95% CI, 11.98-618.08), vaginal intraepithelial neoplasia grade 3 (IRR = 25.65, 95% CI, 10.5-62.69) and oropharyngeal cancer (IRR = 5.51; 95% CI, 1.22-24.84).

Compared with controls, women with a previous CIN3 diagnosis had short- and long-term increased risk for development of HPV-related carcinomas and premalignancies based on age-adjusted IRR stratified by time intervals. The IRR for any HPV-related carcinoma or premalignancy decreased over time but remained elevated for 20 years.

“Higher alertness for HPV-related lesions in women with CIN3 might be advisable,” Ebisch said. “The preventive effect of prophylactic HPV vaccination on development of these lesions should be further studied.” – by Melinda Stevens

For more information:

Renée M.F. Ebisch, MD, can be reached at Department of Obstetrics & Gynecology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands; email: renee.ebisch@radboudumc.nl.

Disclosure: Ebisch reports no relevant financial disclosures. One researcher reports research funding for their institution from Merck Sharp & Dohme and Roche Diagnostics.

Women maintained an increased risk for premalignancies and carcinomas of the anus, vulva, vagina and oropharynx 20 years after cervical intraepithelial neoplasia grade 3 diagnosis, according to results of a population-based study.

“Patients should be informed on an individual basis about this increased risk,” Renée M.F. Ebisch, MD, PhD candidate in the department of obstetrics and gynecology at Radboud University Medical Center in The Netherlands, told HemOnc Today.

Previous studies indicated women with cervical intraepithelial neoplasia grade 3 (CIN3) had increased risk for carcinomas of the anogenital and head and neck areas. However, whether these patients had an increased risk for high-grade premalignancies after diagnosis had not been reported.

Researchers individually matched 89,018 women (median age at diagnosis, 35 years) diagnosed with CIN3 between 1990 and 2010 — identified from the Dutch nationwide registry of histopathology and cytopathology — with a control group of 89,018 women (median age, 36 years) without CIN3.

Researchers evaluated all subsequent cases of high-risk HPV-associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015.

Of women with a previous CIN3 diagnosis, 299 had HPV-related carcinomas and 634 had HPV-related premalignancies.

The controls accrued 1,262,998 person-years and reported 48 HPV-related carcinomas and 50 HPV-related premalignancies.

Researchers reported incidence rate ratios (IRR) in women with CIN3 of 6.2 (95% CI, 4.6-8.46) for any HPV-related carcinoma, 12.75 (95% CI, 9.56-17) for any HPV-related premalignancy, and 9.68 (95% CI, 7.77-12.05) for any HPV-related carcinoma or premalignancy.

Women with a history of CIN3 had increased incidence of anal cancer (IRR = 3.85; 95% CI, 2.32-6.37), anal intraepithelial neoplasia grade 3 (IRR = 6.68; 95% CI, 3.64-12.25), vulvar cancer (IRR = 4.97; 95% CI, 3.26-7.57), vulvar intraepithelial neoplasia grade 3 (IRR = 13.66; 95% CI, 9.69-19.25), vaginal cancer (IRR = 86.08, 95% CI, 11.98-618.08), vaginal intraepithelial neoplasia grade 3 (IRR = 25.65, 95% CI, 10.5-62.69) and oropharyngeal cancer (IRR = 5.51; 95% CI, 1.22-24.84).

Compared with controls, women with a previous CIN3 diagnosis had short- and long-term increased risk for development of HPV-related carcinomas and premalignancies based on age-adjusted IRR stratified by time intervals. The IRR for any HPV-related carcinoma or premalignancy decreased over time but remained elevated for 20 years.

“Higher alertness for HPV-related lesions in women with CIN3 might be advisable,” Ebisch said. “The preventive effect of prophylactic HPV vaccination on development of these lesions should be further studied.” – by Melinda Stevens

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For more information:

Renée M.F. Ebisch, MD, can be reached at Department of Obstetrics & Gynecology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands; email: renee.ebisch@radboudumc.nl.

Disclosure: Ebisch reports no relevant financial disclosures. One researcher reports research funding for their institution from Merck Sharp & Dohme and Roche Diagnostics.