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HPV link to breast, oesophageal cancers in Pretoria study

The findings of multiple human papillomavirus (HPV) co‑infections in patients with breast and oesophageal cancers in a local retrospective study have highlighted the need to broaden the scope of the HPV vaccine to inhibit these cancers, and to include boys in the vaccine campaign.

In 2018, global estimates of cancer reached 18.1m new cases and 9.1m deaths, with a meta‑analysis from 1990-2017 indicating that the burden of cancer quantified as disability‑adjusted life‑years had risen from sixth place in 1990 to second in 2017.

Breast carcinoma is the most prevalent cancer among women worldwide, and the link between the HPV with cervical and other genital squamous cell carcinomas is well established, say researchers from the University of Pretoria in an SA Medical Journal report.

Yet while a number of worldwide studies have identified the presence of HPV infection in patients with breast cancer, others have failed to demonstrate this association.

Oesophageal squamous cell carcinoma (OSCC) is a significant public health problem in many countries, including South Africa, and persistent HPV infection has been implicated  in a number of areas, especially those with a high OSCC prevalence.

The researchers said HPV oncogene products can inhibit tumour suppressor genes such as p53 and retinoblastoma protein (pRb), inhibit antigen presentation and effective local immune response, and induce carcinogenic host cell somatic mutations and genomic instability: these changes have also been observed in breast cancer.

Few reports

Because there are no scientific reports on the association between HPV infection and breast cancer in sub‑Saharan Africa or SA, and a paucity of reports on the association of HPV with OSCC in the region, the cross‑sectional study was undertaken to investigate the presence and genotypes of HPV infections in patients both breast cancer and OSCC, the leading causes of cancer deaths among women and men, respectively, in southern Africa.

The analysis involved patients with confirmed BC or OSCC who had been treated at Steve Biko Academic Hospital in Pretoria from 2015 to 2019. Medical records were accessed, and patient demographic details recorded and pathological samples taken.

Of the total of 151 patients, 101 had breast cancer and 50 had oesophageal squamous cell carcinoma – OSCC). All 101 breast cancer patients were female, with a mean age of 56.2 (15.7) years (range 19-96).

Seventy‑eight BC patients (77.2%) tested positive for HPV infection, with the most infections being in the middle age range (50‑65 years). There were 26 male and 16 female OSCC patients (sex was not stated in eight patient records and could not be deduced from names), with a mean (SD) age of 51.9 (25.7) years (range 18‑88). Forty‑five OSCC patients (90.0%) tested positive for HPV infection, with the highest HPV infection rate also being in the middle age range (50‑65 years)

HPV infection affects >60% of young women in SA, and the scientists hope that the demonstration of infection in patients with these cancers, especially breast cancer, will motivate for expansion of HPV vaccination – currently limited to girls for the prevention of cervical cancer – to include prevention of breast cancer and OSCC, and to be extended to boys as well.

The researchers also suggested a tailor‑made polyvalent vaccine should be designed to include HPV 70, 51, 82 and 35 genotypes in addition to HPV 16 and 18 in a nanovalent HPV vaccine, or at the very least, a pentavalent HPV vaccine incorporating HPV 16, 51, 70, 82 and 35, for it to be completely effective in the prevention of breast or oesophageal cancer in our region.

The paucity of HPV 18 in both BC (5.0%) and OSCC (2.0%) in the present study is noteworthy and diminishes its relevance and importance in the design of vaccines specifically aimed at these cancer types in the region.

They acknowledged a limitation of the study was that it examined HPV genotype profiles at a single academic institution, and its findings might therefore need to be confirmed in other parts of the country.

Study details

Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria

N Maroga, T Mokoena, N Ledibane, A Musekiwa, M Bida, M Kgomo, R Lebelo.

Published in the SA Medical Journal in July 2023

Background

The association between human papillomavirus (HPV) and cervical cancer is well established, and cervical cancer can be prevented through HPV vaccination. Little has been reported on the association between HPV and breast carcinoma (BC) or oesophageal squamous cell carcinoma (OSCC) in Africa. It is possible that use of appropriate HPV vaccines against genotypes responsible for these cancers may also prevent their development.

Objectives
To investigate HPV genotype prevalence in BC and OSCC patients in Pretoria, South Africa (SA).

Methods
A retrospective cross‑sectional study of BC and OSCC patients managed at Steve Biko Academic Hospital from 2015 to 2019 was undertaken. Patient medical records were analysed, and DNA was extracted from their archived pathology material and amplified by polymerase chain reaction before hybridisation for HPV genotypes.

Results
There were 101 patients with BC and 50 with OSCC. The prevalence of HPV infection in BC patients was 77.2%, with 35.6% high‑risk (HR) genotypes, and that in OSCC patients 90.0%, with 56.0% HR genotypes. The most prevalent HPV genotypes (>20% each) were HPV 16, 70 and 51 for BC and HPV 51, 70, 16 and 82 for OSCC, with 31.7% and 60.0% of patients, respectively, having co‑infection with ≥2 genotypes.

Conclusion
The high prevalence of infection with multiple HPV genotypes in BC and OSCC patients, with HPV 16, 51, 70, 35 and 82 the most common genotypes in these cancers, warrants expansion of the current SA bivalent HPV 16/18 vaccine for girls to include boys, and inclusion of HPV 51, 70, 35 and 82, to prevent BC and OSCC as well as cervical cancer.

 

SA Medical Journal article – Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria, South Africa (Creative Commons Licence)

 

See more from MedicalBrief archives:

 

SA makes strides with HPV vaccine campaign, but not fast enough

 

HPV vaccine shows success in gay and bisexual men — HYPER2 study

 

One HPV jab effective for three years, gold-standard Kenya trial finds

 

HPV vaccine cuts cervical cancer by nearly 90% — UK population registry study

 

 

 

 

 

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