Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia: a nationwide population-based cohort study in Denmark.
Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited.



We established a nationwide cohort of approximately 2,500,000 Danish women born in 1918-1990. By linking the cohort to population-based health registries, we obtained information on CIN3/AIS, cancer, migration, death, education, and smoking. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the association between CIN3/AIS and risk of head-and-neck squamous cell carcinoma (HNSCC). HRs were presented for any HNSCC and for four subgroups categorized by their anticipated degree of association with human papillomavirus (HPV).



A history of CIN3/AIS was significantly associated with an increased overall relative risk of HNSCC after adjustment for year of birth, attained age, and length of education. The risk was especially high for sites anticipated to be strongly associated with HPV (e.g. base of tongue, tonsils) (HR, 2.49; 95% CI, 1.84-3.36). Lower risks were found for sites anticipated to be not or weakly associated with HPV (e.g. nasal cavity, middle ear, sinuses) (HR, 1.29; 95% CI, 0.61-2.76).



Women with a history of CIN3/AIS have a significantly higher risk of HNSCC than women without such a history. The increased relative risk persisted for at least 20years after the CIN3/AIS diagnosis. Women with CIN3/AIS may be more susceptible to the consequences of HPV and/or may have higher risk behavior, such as smoking.
Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, Copenhagen, Denmark.
M F
MF
Svahn
Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, Copenhagen, Denmark.
C
C
Munk
Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark.
S M
SM
Jensen
Department of ORL, H&N surgery and audiology, Rigshospitalet, Copenhagen University Hospital, Denmark.
C
C
von Buchwald
Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark.
K
K
Frederiksen
Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, Copenhagen University Hospital, Denmark. Electronic address: susanne@cancer.dk.
S K
SK
Kjaer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology*; D006801:Humans; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology*
Cervical intraepithelial neoplasia; Follow-up; Head-and-neck-cancer; Human papillomavirus