Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia

BACKGROUND: The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2–3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients. METHODS: 3184 patients surgically treated for CIN2–3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population. RESULTS: 173 second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2–3 was 2.2 (CI 95% 1.89–2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR = 1.8; 0.04–10.0), 3 vagina (SIR = 12.4; 2.56–36.3), 1 vulva (SIR = 1.7; 0.04–9.59), 5 oropharynx (SIR = 8.5; 2.76–19.8). Significant risk has been also recorded for pulmonary (SIR = 3.1; 0.70–5.27) and bladder (SIR = 4.05; 1.10–10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR = 2.4; 2.07–2.84) and ovarian cancers (SIR = 2.1; 1.13–3.49), probably due to an higher adherence to spontaneous and programmed screening programs. CONCLUSIONS: Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.