CORRESPONDENCE

Role of human papillomavirus in cancers

To the Editor: With my interest piqued, I read the article in SAMJ by Maroga et al. on the 'Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria, South Africa.'^[1] Studies such as these are essential in investigating the causative factors associated with cancers, especially in our region, where more data are required to inform us on the epidemiology of cancers. However, the role of human papillomavirus (HPV) in breast cancer and oesophageal cancer is not clearly established. This is in contrast to cervical cancer, anal cancer, penile cancer, vaginal cancer, vulvar cancer and oropharyngeal cancer, in which there is proven causation by HPV.P1

HPV is ubiquitous, with infections found worldwide. The presence of HPV DNA alone could be coincidental and not directly related to the cancer, or it could be a co-factor. Transcriptionally active HPV in the form of HPV E6/E7 mRNA detection is the gold standard for clinically relevant oncogenic HPV.^[3] It would have been valuable if other methods were employed in the study, such as p16 immunohistochemistry, HPV E6/E7 mRNA or RNA in situ hybridisation. This would add more strength to the findings. However, many of these methods are HPV type-specific, commonly targeting HPV16 and HPV18, and this study detected a wide range of other high-risk HPV types. The significance of these findings and the high prevalence of HPV co-infection are interesting to explore further.

HPV16 is most frequently associated with HPV-related cancers globally.^[4] In the study, it is noteworthy that other high-risk HPV types were more common or as frequently found as HPV16. In particular, HPV70 and HPV82, which were frequently detected in the study, are classified as group 2b carcinogens (possibly carcinogenic), compared with HPV16 and HPV51, which are group 1 carcinogens.^[5] Most studies from South Africa (SA) on HPV genotype distribution in cervical cancers found that HPV16 was predominant.^[6-9] There was also detection of a substantial proportion of other high-risk HPV types, including HPV18, 33, 35, 39, 45 and 56, as well as infection with multiple high-risk HPV types.^[6-9] Lebelo et al.^[8] showed that there were higher HPV16 viral loads in cervical cancers with co-infections, suggesting HPV16 as the cancer driver.

Safe and effective vaccines are available for prevention of HPV. Besides the use of the bivalent vaccine in the school-based programme targeting young girls before exposure to HPV, studies have shown benefits in catch-up vaccination in older age groups as well as vaccinating males.^[101 Although there is some cross-protection with the bivalent vaccine, use of the nonavalent vaccine, which covers HPV6, 11, 16, 18, 31, 33, 45, 52 and 58 has been modelled, to be cost-effective in SA.^[111 The burden of genital warts and recurrent respiratory papillomatosis in SA necessitates the need to include HPV6 and 11. Mbulawa et al.^[91 highlighted the role of HPV35 in cervical intraepithelial neoplasia and cancer in SA, which is not covered by the current vaccines.

Optimal HPV vaccine coverage and widespread implementation of HPV testing into our cervical cancer screening programme must be our priority to reduce HPV-related diseases.

Aabida Khan

Department of Virology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, and National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, Durban, South Africa KhanA2@ukzn.ac.za

References

1. Maroga N, Mokoena T, Ledibane N, et al. Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria, South Africa. S Afr Med J 2023;113(7):49-54. https://doi.org/10.7196/SAMJ.2023.v113i7.560        [ Links ]

2. Schiffman M, Doorbar J, Wentzensen N, et al. Carcinogenic human papillomavirus infection. Nature Rev Dis Prim 2016;2(1):1-20. https://doi.org/10.1038/nrdp.2016.86        [ Links ]

3. Burd EM. Human papillomavirus laboratory testing: The changing paradigm. Clin Microb Rev 2016;29(2):291-319. https://doi.org/10.1128/cmr.00013-15        [ Links ]

4. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). 2023. Human Papillomavirus and Related Diseases Report. https://hpvcentre.net/statistics/reports/XWX.pdf/ (accessed 28 July 2023).         [ Links ]

5. International Agency for Research on Cancer. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Mon Eval Carcinogenic Risks Hum 2012;100B:1-441. https://www.ncbi.nlm.nih.gov/books/NBK304348/ (accessed 24 July 2023).         [ Links ]

6. Kay P, Soeters R, Nevin J, Denny L, Dehaeck CM, Williamson AL. High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia. J Med Virol 2003;71(2):265-273. https://doi.org/10.1002/jmv.10479        [ Links ]

7. Denny L, Adewole I, Anorlu R, et al. Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa. Int J Cancer 2014;134(6):1389-1398. https://doi.org/10.1002/ijc.28425        [ Links ]

8. Lebelo RL, Bogers JJ, Thys S, et al. Detection, genotyping and quantitation of multiple HPV infections in south African women with cervical squamous cell carcinoma. J Med Virol 2015;87(9):1594-1600. https://doi.org/10.1002/jmv.24132        [ Links ]

9. Mbulawa ZZ, Phohlo K, Garcia-Jardon M, Williamson AL, Businge CB. High human papillomavirus (HPV)-35 prevalence among South African women with cervical intraepithelial neoplasia warrants attention. PloS ONE 2022;17(3):e0264498. https://doi.org/10.1371/journal.pone.0264498        [ Links ]

10. Williamson AL. Recent developments in human papillomavirus (HPV) vaccinology. Viruses 2023;15(7):1440. https://doi.org/10.3390/v15071440        [ Links ]

11. Michaeli DT, Stoycheva S, Marcus SM, Zhang W, Michaeli JC, Michaeli T. Cost-effectiveness of bivalent, quadrivalent, and nonavalent HPV vaccination in South Africa. Clin Drug Invest 2022;42(4):333-343. https://doi.org/10.1007/s40261-022-01138-6        [ Links ]