A descriptive study of human papilloma virus in upper aero-digestive squamous cell carcinoma at Uganda cancer institute assessed by P16 immunohistochemistry

Abstract

Background: Cancer burden in sub-Saharan Africa is on the rise with one-third of cancers estimated to be caused by infectious agents. Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy in sub-Saharan Africa and includes tumors in the Upper Aero-digestive Tract (UADT). The established risk factors are tobacco and alcohol exposure with a recent recognition of the role of Human Papilloma Virus (HPV). The HPV related HNC is seen predominantly in the oropharynx, presents at a younger age and has a better prognosis. With a rapidly increasing incidence of these cancers in the developed world, it was important to study HPV in HNC in Uganda. The HPV can be detected using P16 immunohistochemistry as a surrogate marker thus making it suitable for screening. The study aimed at establishing the presence of HPV and the commonly affected sites in UADT squamous cell carcinoma (SCC) at Uganda Cancer Institute (UCI) using P16 immunohistochemistry. Methodology: This was a cross sectional study in which 59 patients with histologically proven SCC from the oral cavity, oropharynx, larynx and hypopharynx were recruited. These patients' demographics and clinical data were collected. Tissue sections from retrieved histology samples were stained by Haematoxylin and Eosin to reconfirm SCC. Subsequently, P16 expression was determined using P16 immunohistochemistry. Results: Seventy-one patients were enrolled and 59 patients with confirmed SCC of the sites of interest were analyzed. The majority (79.7%) of the participants were male and over 50 years. 59.3% were tobacco smokers, 66.1% used alcohol, 52.2% used both. Only 27.1% used none of the substances. Only 27.1% of the participants were HIV positive. Most of the tumors were in the larynx (37.3%) and 64.4% were overall TNM stage 4. The overall prevalence of HPV in UADT SCC at UCI was 20.3, 95%CI 10.9-32.8. The oropharynx had the highest prevalence (30.8%). Conclusion: The prevalence of HPV in UADT SCC at UCI is significant at 20.3%. The most affected site, is the oropharynx. Vigilant HPV screening of these sites with confirmation where possible is recommended.

The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma

“…Thirty-one studies met the inclusion criteria, comprising 5007 patients with OCSCC from 24 different countries. Sixteen studies were from Asia [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], eight from Europe [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], two from Africa [ 43 , 44 ], two from South America [ 35 , 45 ], two from North America [ 46 , 47 ], and one from Asian Pacific [ 48 ]. The study size ranged from 17 patients in a study from Uganda [ 44 ] to 940 patients in the Netherlands [ 41 ].…”

“…Data regarding HPV+ OCSCC association with clinical characteristics could not be extracted from seventeen studies either because it was not described or the data was pooled on multiple anatomical locations in HNSCC [ 19 , 20 , 22 , 24 , 25 , 26 , 29 , 31 , 32 , 33 , 39 , 40 , 42 , 43 , 44 , 46 , 47 ].…”

A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide

“…HPV detection methods varied among the included studies. Fifteen studies were based on double positivity with both HPV DNA PCR and p16 IHC ( n = 6624) [ 4 , 16 , 19 , 20 , 22 , 23 , 28 , 30 , 32 , 33 , 34 , 35 , 38 , 39 , 40 ], eight studies were based on HPV DNA alone ( n = 426) [ 12 , 14 , 15 , 24 , 25 , 29 , 36 , 41 ], six on p16 alone ( n = 391) [ 17 , 18 , 21 , 26 , 27 , 31 ], one study was based on both HPV DNA and HPV RNA ( n = 99) [ 37 ] and one study did not report a detection method ( n = 42,024) [ 13 ]. Most studies using p16 IHC defined p16-positivity (p16+) according to ASCO guidelines with ≥70% positive staining [ 42 ] ( n = 2663), but one study defined p16+ as ≥10% positive staining ( n = 30) [ 30 ], four studies defined p16+ as ≥75% positive staining ( n = 2678) [ 4 , 22 , 31 , 32 ] and one study did not account for p16-positivity ( n = 926) [ 35 ].…”

“…A higher occurrence of HPV+ OPSCC in northern European countries than in outhern European countries has also been reported previously [ 11 , 43 ]. Twenty-two of the included studies observed a greater incidence of HPV− OPSCC than HPV+ OPSCC, distributed in Europe, South America, Africa, The Middle East, and Asia-Pacific [ 14 , 16 , 17 , 18 , 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. The lowest HPV prevalence was observed in India (0%), but this study comprised only 20 patients and had a very high frequency of alcohol (80%), smoking (80%), betel nut chewing (75%), and beedi smoking (90%) [ 14 ].…”

“…When studies addressed other oropharyngeal sites besides TSCC and BTSCC, the overall HPV prevalence would therefore be lower than if only TSCC/BTSCC were included. Additionally, 12 studies did not address anatomical sublocations [ 12 , 14 , 16 , 17 , 18 , 25 , 26 , 27 , 31 , 39 , 40 , 41 ]. This variation in reporting and including specific anatomical subsites complicates comparison between studies.…”