Diversity of HPV types in cancerous and pre‐cancerous penile lesions of South African men: Implications for future HPV vaccination strategies

Lebelo, Ramokone L.; Boulet, Gaëlle; Nkosi, Cornelius M.; Bida, Mechack N.; Bogers, Johannes; Mphahlele, M. Jeffrey

doi:10.1002/jmv.23730

Cited by 22 publications

(15 citation statements)

References 31 publications

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“…Five of 4 μm sections were cut using microtome and placed in sterile 2 ml Cryotube polypropylene with screw cap tubes at room temperature before testing. Total DNA was extracted using the NucleoSpin Tissue extraction kit following manufacturer's protocol (Macherey‐Nagel, Germany) as described [Lebelo et al, ]. All 90 samples were subjected to TaqMan‐based qPCR essentially as described [Micalessi et al, ; Lebelo et al, ] on LightCycler 480 II system (Roche Diagnostics, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

“…Total DNA was extracted using the NucleoSpin Tissue extraction kit following manufacturer's protocol (Macherey‐Nagel, Germany) as described [Lebelo et al, ]. All 90 samples were subjected to TaqMan‐based qPCR essentially as described [Micalessi et al, ; Lebelo et al, ] on LightCycler 480 II system (Roche Diagnostics, Basel, Switzerland). The TaqMan‐based quantitative qPCR enables the detection of 80 bp fragment of 13 HR types (HPV 16 E7, HPV 18 E7, HPV 31 E6, HPV 33 L1, HPV 35 E6, HPV 39 E7, HPV 45 E7, HPV 51 E7, HPV 52 E7, HPV 56 E7, HPV58 E6, HPV 59 E7, HPV 68 E7), two probable HR types (HPV 53 E6 and HPV 66 E6), two LR types (HPV 6 E6 and HPV 11 E6) and one undetermined risk type (HPV 67 L1) and human β‐globin [Micalessi et al, ].…”

Section: Methodsmentioning

confidence: 99%

“…The lysates were then subjected to TaqMan‐based quantitative type‐specific qPCR [Micalessi et al, ] on LightCycler 480 II system (Roche Diagnostics, Basel, Switzerland) as described [Lebelo et al, ] with minor modifications; final reaction volume of 25 μl (20 μl of master mix and 5 μl lysate). The thermocycling conditions were also the same as previously reported [Micalessi et al, ; Lebelo et al, ]. HPV 11 PCR was performed in a different master mix containing HPV 11 primers and probes however qPCR system and protocol was the same as reported [Micalessi et al, ].…”

Section: Methodsmentioning

confidence: 99%

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Detection, genotyping and quantitation of multiple hpv infections in south african women with cervical squamous cell carcinoma

et al. 2015

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In Africa, data is limited on quantitation of human papillomavirus (HPV) types in women with multiple infections. This study applied a real time PCR (qPCR) assay for detection, genotyping and quantitation of multiple HPV infections in 90 tissue blocks of South African women with cervical squamous cell carcinoma. One sample with multiple HPV types was subjected to laser micro-dissection and qPCR. Four samples were negative for β-globin and these were excluded from the analysis. The HPV DNA positivity rate was 93.0% (80/86). All 80 positives showed the presence of HR HPV types; HPV 68 was the only type negative in all the samples. Overall, HPV 16 was positive in most of the samples (88.8%), followed by HPV 56 (28.7%), HPV 18 (20.0%) and HPV 39 (18.7%). More than half of the samples (65.0%) had multiple infections. HPV 16 was present in majority of single (85.7%) and multiple infections (90.4%). HPV 16 showed higher viral loads in 70.3% of the HPV 16 co-infected samples. In one multiple infected sample laser micro-dissection and qPCR identified HPV 18 with higher viral load as the most likely cause of the invasive lesion. There is large number of multiple HPV infections in South African women with cervical squamous cell carcinoma. HPV 16 is the most frequently detected type and often presents with higher viral load, suggesting it could be responsible for pathogenesis of the lesions in the majority of cases.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Detection, genotyping and quantitation of multiple hpv infections in south african women with cervical squamous cell carcinoma

et al. 2015

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“…A recent study has shown that from a cohort men aged 16–20 years old who have sex with men, 39% tested positive for HPV DNA, with 23% testing positive for the vaccine subtypes 6, 11, 16 and 18 . Similarly, a study in South Africa found that 80% of penile precancerous lesions were positive for HPV11 while 62.9% of cancerous lesions were positive for HPV16 with some lesions testing positive for several types . Testing of the quadrivalent Gardasil vaccine in males aged 16–26 indicated >80% efficacy (per protocol population) in protecting against genital lesions and persistent infection with vaccine genotypes .…”

Section: Prophylactic Vaccinesmentioning

confidence: 99%

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against highrisk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd. INTRODUCTIONTargeting cancers for immunotherapy is often complicated by a lack of immunogenic tumour peptides. Mutated or overexpressed self-antigens are frequently the targets and invoke a generally low affinity/avidity T and B cell response. In contrast, the tight association between infection with HPV and cervical cancer means that foreign viral proteins encoded by HPV can provide the basis of either prophylactic or therapeutic cancer vaccines [1,2]. The natural course of anogenital HPV infection results in overwhelming clearance of the virus in 98% of individuals with an immune component suggested by the increased risk of HPV-associated cancers in immune-compromised organ transplant recipients [3,4]. However, HPV genotype-specific antibodies against the viral capsid proteins (L1 and L2) are produced at only low levels in about half the patients, can take close to a year to develop after natural infection and associate with higher viral loads in the cervix [5]. Thus, natural antibody may reflect the non-lytic, localised, intracellular nature of the infection leading to poor immunogenicity for immunoglobulin production and a greater emphasis on T-cell immunity for viral clearance. In contrast, prior immunization with HPV capsid proteins in animal studies induces high titres of antibody that are protective against challenge infection. Early studies in dogs demonstrated that prior immunization with L1 capsid protein could protect beagles from mucosal challenge with canine oral ...

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“…[59] Data from Zimbabwe suggest that southern Africa has higher incidence rates, [60] and a recently published report of HPV detection in cancerous and precancerous penile lesions from men in South Africa demonstrated multiple HPV infections, with high rates of HPV-16. [61] Risk factors for penile cancer include: a lack of MC; phimosis and/or poor genital hygiene; AGWs; and HIV infection. HIV-positive men have an eight-fold increased risk of penile cancer, which may be associated with higher HPV infection rates.…”

Section: Penile Cancermentioning

confidence: 99%

Human papillomavirus infection and disease in men: Impact of HIV

Delany‐Moretlwe

Chikandiwa

Gibbs

2013

South. Afr. j. HIV med.

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There is growing evidence of a significant burden of human papillomavirus (HPV) infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly associated with the development of anogenital warts and anal, penile and head and neck cancers in men. Despite increasing access to antiretroviral therapy, there appears to be little benefit in preventing the development of these cancers in HIV-positive men, making prevention of infection a priority. New prevention options that are being introduced in many African countries include male circumcision and HPV vaccination. However, more data are needed on the burden of HPV disease in men before boys are included in HPV vaccination programmes. Human papillomavirus (HPV) is a common sexually transmitted infection (STI) affecting both men and women. S Afr J HIV Med[1] HPV infections can be classified as either low-(LR) or high-risk (HR).[2]HR-HPV infections have been associated with cancer of the anogenital and oropharyngeal tissues. While the majority of HPV infections are transient and clear spontaneously, persistent infection with HR-HPV is associated with the development of pre-neoplastic and neoplastic lesions in these areas (Fig. 1). While much is known about the natural history of HPV infection in cervical cancer in women, less is known about the development of HPV-associated disease in men. Emerging evidence points to a significant role for HIV infection in promoting HPV prevalence, incidence and persistence. This review provides an update on current evidence regarding the epidemiology of HPV infection and disease in men, the effects of HIV on HPV infection and disease in men in sub-Saharan Africa (SSA), and the prospects for prevention in this setting. Global burden of HPVHPV infection is ubiquitous in men. A systematic review of 62 studies using reliable methods of HPV DNA detection and conducted prior to 2009, representing 14 800 men in 23 countries, showed that anogenital HPV DNA prevalence is generally high in sexually active men. The review highlighted considerable variation in estimates by region, from 1% to 84% in LR men, to 2% to 93% in HR men. [3] Compared with studies in women, peak prevalence spanned a wide range of ages, suggesting that men have the potential for longer-term persistence of infection or higher rates of re-infection.[3] Typespecific HPV seroprevalence studies are better indicators of lifetime exposure to HPV infection, although they may underestimate cumulative HPV exposure, given that not all infections lead to seroconversion.[4] Recent population-based studies have estimated the prevalence of antibodies to vaccinepreventable HPV types 6, 11, 16 and 18. Among men aged 14 -59 years in the USA, 12.2% of men were seropositive for any vaccine type, with a peak prevalence of 18% among men aged 50 -59 years.[5] In a similar population-based study in Australia, peak prevalence of any...

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Diversity of HPV types in cancerous and pre‐cancerous penile lesions of South African men: Implications for future HPV vaccination strategies

Cited by 22 publications

References 31 publications

Detection, genotyping and quantitation of multiple hpv infections in south african women with cervical squamous cell carcinoma

Detection, genotyping and quantitation of multiple hpv infections in south african women with cervical squamous cell carcinoma

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

Human papillomavirus infection and disease in men: Impact of HIV

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