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Second primary anal and oropharyngeal cancers in cervical cancer survivors

      Background

      Human papilloma virus infection is responsible for approximately 31,500 new cancers in the United States annually. Almost all cervical cancers are linked to human papilloma virus infection. As early identification and treatment of cervical cancer improve, the incidence of cervical cancer has decreased and survival has improved. However, survivors continue to remain at risk for other human papilloma virus–related malignancies. The purpose of this study was to assess the risk of primary anal and oropharyngeal cancers among women with a history of squamous cell carcinoma of the cervix.

      Study Design

      A population-based cohort of 21,060 women diagnosed with cervical squamous cell carcinoma from 1973 through 2014 was identified from the Surveillance, Epidemiology, and End Results Program-9 data. Standardized incidence ratios for anal and oropharyngeal cancers were calculated to estimate the risk of a second primary human papilloma virus–related malignancy based on incidence in the general population. Results were further stratified by age (20–53, 54 years old or older) and latency period (2–11, 12–59, 60–119, 120 months or longer). The number needed to screen for oropharyngeal and anal cancers was estimated using study results and Centers for Disease Control and Prevention–reported incidence rates.

      Results

      Cervical squamous cell cancer survivors had a higher risk of being diagnosed with oropharyngeal cancer (standardized incidence ratio, 4.36, 95% confidence interval, 1.19–11.15) and anal cancer (standardized incidence ratio, 2.20, 95% confidence interval, 1.28–3.52). Patients diagnosed with cervical cancer between ages 20 and 53 years had an increased risk of anal cancer (standardized incidence ratio, 3.53, 95% confidence interval, 1.15–8.23). Age 54 years or older at cervical cancer diagnosis was associated with increased oropharyngeal cancer risk only (standardized incidence ratio, 5.04, 95% confidence interval, 1.37–12.91). Latency stratification was significant for increased OPC risk between 2–11 months and 12–59 months after diagnosis. At 120 months or longer, there was an increased risk of both oropharyngeal cancer (standardized incidence ratio, 7.97, 95% confidence interval, 2.17–20.42) and anal cancer (standardized incidence ratio, 2.60, 95% confidence interval, 1.34–4.54). The estimated number needed to screen for oropharyngeal cancer (number needed to screen for oropharyngeal cancer, 282) and anal cancer (number needed to screen for anal cancer, 1272) is significantly less than the number needed to screen for cervical cancer.

      Conclusion

      Squamous cell cervical cancer survivors have a substantially increased risk of anal and oropharyngeal cancers. This increased risk is significant 10 or more years after the cervical cancer diagnosis. Health care providers and survivors should be aware of this increased risk. The development of effective and economical surveillance methods for anal and oropharyngeal cancers in cervical cancer survivors is urgently needed.

      Key words

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      References

        • Viens L.J.
        • Henley S.J.
        • Watson M.
        • et al.
        Human papillomavirus-associated cancers – United States, 2008–2012. Centers for Disease Control and Prevention.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 661-666
        • Salani R.
        • Khanna N.
        • Frimer M.
        • Bristow R.E.
        • Chen L.
        An update on post-treatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations.
        Gynecol Oncol. 2017; 146: 3-10
        • Chaturvedi A.K.
        • Engels E.A.
        • Gilbert E.S.
        • et al.
        Second cancers among 104,760 survivors of cervical cancer: Evaluation of long-term risk.
        J Natl Cancer Inst. 2007; 99: 1634-1643
        • Chaturvedi A.K.
        Beyond cervical cancer: burden of other HPV-related cancers among men and women.
        J Adolesc Health. 2010; 46: S20-S26
        • Berman T.A.
        • Schiller J.T.
        Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases.
        Cancer. 2017; 123: 2219-2229
        • American Cancer Society
        Oral cavity and orophayngeal cancer—key statistics.
        (Available at:)
        • Crawford R.
        • Grignon A.
        • Kitson S.
        • et al.
        High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology.
        BMC Cancer. 2011; 11: 473
        • Medford R.J.
        • Salit I.E.
        Anal cancer and intraepithelial neoplasia: epidemiology, screening and prevention of a sexually transmitted disease.
        CMAJ. 2015; 187: 111-115
      1. NIH National Cancer Institute. 2018. Cancer Stat Facts. Available at: https://seer.cancer.gov/statfacts/. Accessed September 1, 2018.

        • Neumann F.
        • Jégu J.
        • Mougin C.
        • et al.
        Risk of second primary cancer after a first potentially-human papillomavirus-related cancer: a population-based study.
        Prev Med. 2016; 90: 52-58
        • Sand F.L.
        • Munk C.
        • Jensen S.M.
        • Svahn M.F.
        • Frederiksen K.
        • Kjaer S.K.
        Long-term risk for noncervical anogenital cancer in women with previously diagnosed high-grade cervical intraepithelial neoplasia: a Danish nationwide cohort study.
        Cancer Epidemiol Biomarkers Prev. 2016; 25: 1090-1097
        • Ebisch R.
        • Rutten D.
        • IntHout J.
        • et al.
        Long-lasting increased risk of human papillomavirus-related carcinomas and premalignancies after cervical intraepithelial neoplasia grade 3: a population-based cohort study.
        J Clin Oncol. 2017; 35: 2542-2550
        • Edgren G.
        • Sparen P.
        Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study.
        Lancet Oncol. 2007; 8: 311-316
        • Ragin C.
        • Taioli E.
        Second primary head and neck tumor risk in patients with cervical cancer—SEER Data analysis.
        Head Neck. 2008; 30: 58-66
        • Balamurugan A.
        • Ahmed F.
        • Saraiya M.
        • et al.
        Potential role of human papillomavirus in the development of subsequent primary in situ invasive cancers among cervical cancer survivors.
        Cancer. 2008; 113: 2919-2925
        • Matsuo K.
        • Blake E.A.
        • Machida H.
        • Mandelbaum R.S.
        • Roman L.D.
        • Wright J.D.
        Incidences and risk factors of metachronous vulvar, vaginal, and anal cancers after cervical cancer diagnosis.
        Gynecol Oncol. 2018; 150: 501-508
        • Rembold C.M.
        Number needed to screen: development of a statistic for disease screening.
        BMJ. 1998; 317: 307-312
        • Landy R.
        • Castanon A.
        • Hamilton W.
        • et al.
        Evaluating cytology for the detection of invasive cervical cancer.
        Cytopathology. 2016; 27: 201-209