Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia
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RESEARCH ARTICLE
Open Access
Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia Mario Preti1, Stefano Rosso2, Leonardo Micheletti1, Carola Libero1, Irene Sobrato2, Livia Giordano3, Paola Busso2, Niccolò Gallio1* , Stefano Cosma1, Federica Bevilacqua1 and Chiara Benedetto1
Abstract 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. Keywords: HPV-related cancers, Anogenital area, Anal cancer, Vaginal cancer, Vulvar cancer, Multiple subsequent cancers
Background High-risk human papillomaviruses (hrHPV) are estimated to cause 5.2% of all cancers worldwide, with HPV16 alone responsible for approximately 70% of cervical cancer, that is the first most common HPV-related cancer in women [1]. HPV are also detectable in 15– 48% of vulvar, 68–86% of vaginal, 85–91% of anal,19– * Correspondence: [email protected] 1 Department of Surgical Sciences University of Torino, Via Ventimiglia 3, 10126 Torino, Italy Full list of author information is available at the end of the article
25% of oropharyngeal, 3–5% of oral cavity, 2–5% of larynx cancers [2–5]. Precancerous lesions precede these cancers, and cervical intraepithelial neoplasia (CIN) is the most studied and treated. Despite CIN treatment has a high impact in reducing cancer risk (from 95 to 99%), treated women are still considered at higher risk of cervical malignancies compared to the general population and at risk of HPVrelated malignancies in other body sites [6, 7]. Many studies demonstrated that women with history of diagnosis and treatment for high-grade CIN
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