Anal cancer risk: HPV-based cervical screening programmes
Authors: Ulrike Wieland, Alexander Kreuter
Journal: The Lancet Infectious Diseases (2019)

Similar to cervical cancer, most anal cancers (89–100%) are induced by persistent infections with high-risk human papillomavirus (HPV), especially HPV16.1Lin C Franceschi S Clifford GM Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis.Lancet Infect Dis. 2018; 18: 198-206Summary Full Text Full Text PDF PubMed Scopus (182) Google Scholar Anal cancer accounts for only 4% of all malignancies of the lower alimentary tract, but its incidence is rising in high-income countries. For the USA, increasing average annual percentage changes of 2·1 for men and 2·9 for women have been reported.2Van Dyne EA Henley SJ Saraiya M Thomas CC Markowitz LE Benard VB Trends in human papillomavirus-associated cancers—United States, 1999–2015.MMWR Morb Mortal Wkly Rep. 2018; 67: 918-924Crossref PubMed Scopus (234) Google Scholar About 8300 new anal cancer cases are diagnosed in the USA each year, with higher incidence rates in women than in men.3PDQ Screening and Prevention Editorial Board: anal cancer prevention (PDQ)NCBI bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK179253/Date: March 8, 2019Date accessed: April 10, 2019Google Scholar Similar numbers have been estimated for Europe.4Hartwig S St Guily JL Dominiak-Felden G Alemany L de Sanjosé S Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe.Infect Agent Cancer. 2017; 12: 19Crossref PubMed Scopus (68) Google Scholar More than one-third of patients with anal cancer die within 5 years after diagnosis.3PDQ Screening and Prevention Editorial Board: anal cancer prevention (PDQ)NCBI bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK179253/Date: March 8, 2019Date accessed: April 10, 2019Google Scholar Several risk groups for anal cancer have been identified, such as men who have sex with men, transplant recipients, people with HIV/AIDS, and women with a history of HPV-induced cervical, vaginal, or vulvar cancer.3PDQ Screening and Prevention Editorial Board: anal cancer prevention (PDQ)NCBI bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK179253/Date: March 8, 2019Date accessed: April 10, 2019Google Scholar The latter group has an increased incidence (three to 22 times) of anal cancer, compared with the general population.3PDQ Screening and Prevention Editorial Board: anal cancer prevention (PDQ)NCBI bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK179253/Date: March 8, 2019Date accessed: April 10, 2019Google Scholar Anogenital HPV-induced cancers are largely preventable by prophylactic vaccination of HPV-naive individuals (primary prevention) or by screening for precancers (secondary prevention).5Schiller J Lowy D Explanations for the high potency of HPV prophylactic vaccines.Vaccine. 2018; 36: 4768-4773Crossref PubMed Scopus (84) Google Scholar, 6Morris BJ The advent of human papillomavirus detection for cervical screening.Curr Opin Obstet Gynecol. 2019; published online April 2. DOI:10.1097/GCO.0000000000000542Crossref PubMed Scopus (6) Google Scholar For cervical cancer, population-based cytology screening has been replaced by primary HPV screening or by co-testing (HPV and cytology) in several countries.6Morris BJ The advent of human papillomavirus detection for cervical screening.Curr Opin Obstet Gynecol. 2019; published online April 2. DOI:10.1097/GCO.0000000000000542Crossref PubMed Scopus (6) Google Scholar By contrast, anal cancer screening has been recommended only for high-risk groups, such as HIV-positive individuals, especially men who have sex with men.7Gosens KC Richel O Prins JM Human papillomavirus as a cause of anal cancer and the role of screening.Curr Opin Infect Dis. 2017; 30: 87-92Crossref PubMed Scopus (23) Google Scholar, 8EACSEACS guidelines, version 9.1.http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdfDate: October, 2018Date accessed: April 10, 2019Google Scholar However, the evidence of benefit has yet to be established in ongoing prospective studies.7Gosens KC Richel O Prins JM Human papillomavirus as a cause of anal cancer and the role of screening.Curr Opin Infect Dis. 2017; 30: 87-92Crossref PubMed Scopus (23) Google Scholar In a study in The Lancet Infectious Diseases, Chunqing Lin and colleagues9Lin C Slama J Gonzalez P et al.Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.Lancet Infect Dis. 2019; published online June 13. http://dx.doi.org/10.1016/S1473-3099(19)30164-1Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar have shown that data available from routine HPV-based cervical screening programmes can be used to define anal cancer risk profiles in the participating women. Lin and colleagues did a retrospective collaborative pooled meta-analysis, including individual-level data from 36 studies with 13 427 women for whom paired anal and cervical samples were available. They found that cervical HPV16 is strongly associated with anal HPV16. 41% of HIV-negative women with cervical HPV16 also had anal HPV16, compared with 2% of those without cervical HPV16 (prevalence ratio [PR] 16·5); in HIV-positive women, these values were 46% and 11% (PR 4·4). Anal precancer (high-grade squamous intraepithelial lesion [HSIL]) was associated with cervical high-risk HPV and with cervical HSIL, regardless of HIV status. One quarter of older women (aged >45 years) with cervical HPV16 had anal HPV16-associated HSIL (25% of HIV-negative women, 23% of HIV-positive women).9Lin C Slama J Gonzalez P et al.Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.Lancet Infect Dis. 2019; published online June 13. http://dx.doi.org/10.1016/S1473-3099(19)30164-1Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar Notwithstanding the divergent progression rates of anal HSIL to invasive cancer reported in the literature7Gosens KC Richel O Prins JM Human papillomavirus as a cause of anal cancer and the role of screening.Curr Opin Infect Dis. 2017; 30: 87-92Crossref PubMed Scopus (23) Google Scholar, the findings of Lin and colleagues9Lin C Slama J Gonzalez P et al.Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.Lancet Infect Dis. 2019; published online June 13. http://dx.doi.org/10.1016/S1473-3099(19)30164-1Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar have important public health implications. Anal cancer screening might be advisable in all women with cervical high-risk HPV infection (irrespective of their HIV status), particularly if the detected HPV-type is HPV16. Furthermore, a diagnosis of cervical HSIL or cancer seems to be a strong determinant for anal HSIL, also in HIV-negative women (PR 23·1). In HIV-positive women, anal HSIL was found in 25% of patients with cervical HSIL, but also in 7% of those with normal cervical cytology. Similarly, 8% of HIV-positive women without cervical high-risk HPV infection had anal HSIL. This finding could argue for anal cancer screening in more HIV-positive women than only in those with HPV-associated dysplasia.8EACSEACS guidelines, version 9.1.http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdfDate: October, 2018Date accessed: April 10, 2019Google Scholar Anal cancer screening algorithms for both HIV-negative and HIV-positive women could possibly be further refined by incorporating additional risk factors, such as smoking or sexual practices.3PDQ Screening and Prevention Editorial Board: anal cancer prevention (PDQ)NCBI bookshelf.https://www.ncbi.nlm.nih.gov/books/NBK179253/Date: March 8, 2019Date accessed: April 10, 2019Google Scholar Similar to anal cancer, incidence rates of HPV-associated oropharyngeal cancer are steadily increasing, especially in men, but also in women.2Van Dyne EA Henley SJ Saraiya M Thomas CC Markowitz LE Benard VB Trends in human papillomavirus-associated cancers—United States, 1999–2015.MMWR Morb Mortal Wkly Rep. 2018; 67: 918-924Crossref PubMed Scopus (234) Google Scholar It would be interesting to analyse whether the cervical markers described by Lin and colleagues (HPV16 positivity, HSIL, and cancer)9Lin C Slama J Gonzalez P et al.Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.Lancet Infect Dis. 2019; published online June 13. http://dx.doi.org/10.1016/S1473-3099(19)30164-1Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar are also associated with an increased risk for HPV-induced oropharyngeal cancer. Such studies could be done in countries that maintain comprehensive health databases and cancer registries. However, viable screening tests for HPV-associated oropharyngeal cancer do not yet exist.10Berman TA Schiller JT Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.Cancer. 2017; 123: 2219-2229Crossref PubMed Scopus (168) Google Scholar High-resolution anoscopy is the gold standard for diagnosing anal precancer, but high-resolution anoscopy is not widely available, which could hamper comprehensive screening of high-risk groups beyond HIV-positive individuals.7Gosens KC Richel O Prins JM Human papillomavirus as a cause of anal cancer and the role of screening.Curr Opin Infect Dis. 2017; 30: 87-92Crossref PubMed Scopus (23) Google Scholar HPV vaccination has already led to significant changes in cervical high-risk HPV infection and precancer rates in younger women.11Machalek DA Garland SM Brotherton JML et al.Very low prevalence of vaccine human papillomavirus types among 18- to 35-year old Australian women 9 years following implementation of vaccination.J Infect Dis. 2018; 217: 1590-1600Crossref PubMed Scopus (77) Google Scholar, 12McClung NM Gargano JW Bennett NM et al.Trends in human papillomavirus vaccine types 16 and 18 in cervical precancers, 2008–2014.Cancer Epidemiol Biomarkers Prev. 2019; 28: 602-609Crossref PubMed Scopus (44) Google Scholar The decrease of cervical (and anal) HPV16/18 infection and precancer could make targeted secondary anal cancer prevention feasible despite insufficient resources, especially if high-resolution anoscopy could be preceded by anal high-risk HPV testing. Hopefully, the findings presented by Lin and colleagues9Lin C Slama J Gonzalez P et al.Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.Lancet Infect Dis. 2019; published online June 13. http://dx.doi.org/10.1016/S1473-3099(19)30164-1Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar will encourage the initiation of prospective trials evaluating screening programmes for all women with an elevated risk for anal cancer. AK has received fees for lectures from Merck Sharp & Dohme and InfectoPharm, and has served as an advisory board member for Sanofi Pasteur, Merck Sharp & Dohme, and AbbVie. UW is supported by the German Federal Ministry of Health ( grant number 1369-401 ). Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysisHPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. Full-Text PDF Open Access