Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma

Neale, Rachel E.; Weissenborn, Soenke J.; Abeni, Damiano; Bavinck, Jan Nico Bouwes; Euvrard, Sylvie; Feltkamp, Mariet C.W.; Green, Adèle C.; Harwood, Catherine A.; Koning, Maurits de; Naldi, Luigi; Nindl, Ingo; Pawlita, Michael; Proby, Charlotte M.; Quint, Wim; Waterboer, Tim; Wieland, Ulrike; Pfister, Herbert

doi:10.1158/1055-9965.epi-12-0917-t

Cited by 87 publications

(89 citation statements)

References 27 publications

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“…Briefly, PM-PCR was performed in a final reaction volume of 50 ml, containing 10 ml of the isolated DNA, 2.5 mM MgCl 2 , 1Â GeneAmp PCR buffer II, 0.2 mM deoxynucleoside triphosphates, 1.5 U Amplitaq Gold DNA polymerase and 10 ml of the PM primer mix. The PCR was performed by a 9-min preheating step at 94 1C, followed by 35 …”

Section: B-hpv Dna Detection and Genotyping With The Pm-pcr Reverse Hmentioning

confidence: 99%

“…Seroepidemiological studies have associated skin cancer in organ transplant recipients with the presence of anti-b-HPV antibodies, and PCR-based studies have identified b-HPV DNA in over 80% of skin tumors from these patients. 22,[35][36][37][38][39][40][41][42][43] Despite these findings, a causal role of these viruses has been difficult to verify because of their ubiquitous prevalence in the general population and their absence in some cancers. 25,44 The major weakness of the available studies is that the proposed association is mostly based on the presence of viral DNA in tumor tissues or positive antibody responses.…”

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confidence: 99%

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Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

et al. 2014

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The aim of this study was to determine whether detection of b-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that b-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the b-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that b-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion. Modern Pathology (2014) 27, 1101-1115; doi:10.1038/modpathol.2013.240; published online 3 January 2014Keywords: b-HPV; immunosuppression; kidney transplant recipients; skin cancer; viral life cycle Solid organ transplantation is a treatment offered to an increasing number of patients with end-stage organ diseases. Although lifesaving, organ transplantation is associated with an overall three-to fivefold increased risk of malignancies. 1-4 Most of these cancers are caused by reactivated viruses whose oncogenic potential is suppressed by immunological reactions in healthy individuals, like Epstein-Barr virus-associated B-cell lymphomas, Kaposi's sarcoma, caused by the reactivation of human herpesvirus type 8, and Merkel cell carcinoma of the skin, associated with Merkel cell polyomavirus. [5][6][7][8][9] Of the cancers presenting in organ transplant recipients that have no established infectious etiology, skin cancer is the most frequent form (95%), including squamous and basal cell carcinomas. [10][11][12][13] The incidence of skin cancer, the most common cancer in fair-skinned populations, is at least 50-fold higher in organ transplant recipients. 14-16 Large numbers of skin tumors (often more than 10) tend to develop over time in these at-risk subjects, thus

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Section: B-hpv Dna Detection and Genotyping With The Pm-pcr Reverse Hmentioning

confidence: 99%

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confidence: 99%

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

et al. 2014

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“…Serum was collected and tested for 16 βPV, 6 γPV, 4 αPV, 2 μPV, and 1 νPV IgG antibodies with a multiplex serology technique based on glutathione s‐transferase capture ELISA in combination with fluorescent bead technology 37, 38. All 3 techniques used have been previously described in more detail 25, 32, 35, 36, 37, 38…”

Section: Methodsmentioning

confidence: 99%

“…A substantial body of epidemiologic data show an association between HPV infection and cSCC,12, 20, 21, 22, 23, 24 in particular, in OTRs 25, 26. In most studies, HPV infection has been determined by detection of serologic responses to a large series of βPV and sometimes γPV types12, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31 and less frequently by detecting genomic DNA from 1 or multiple HPV types in eyebrow hair or skin scrapings 20, 21, 25, 32, 33, 34…”

Section: Introductionmentioning

confidence: 99%

“…Case‐control studies in both OTR and immunocompetent populations have shown that the presence of βPV DNA or antibodies was associated with a 1.5‐ to 3‐fold increased risk of cSCC 12, 20, 21, 22, 23, 24, 25, 26, 29, 31, 32. It was not possible, however, to determine whether the βPV infection increases risk of cSCC development or whether cSCC formation promotes active proliferation of βPV.…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Bavinck

Feltkamp

Green

et al. 2018

American Journal of Transplantation

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Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.

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Associations of Oral α-, β-, and γ-Human Papillomavirus Types With Risk of Incident Head and Neck Cancer

et al. 2016

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IMPORTANCE Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of α-, β-, and γ- HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-HPV detection in the oral cavity and incident HNSCC. DESIGN A nested case-control study was carried out among 96 650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n = 132) were identified duringan average 3.9 years of follow-up in both cohorts. Three controls per case (n = 396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection. METHODS Through a next-generation sequencing assay, DNA from α-, β-, and γ-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for β- and γ-HPVs. MAIN OUTCOMES AND MEASURES Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx. RESULTS A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2–22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8–276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6–34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01–834.80). Detection of β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98–56.82; P = .054), oral cavity (OR, 5.34; 95% CI, 1.51–18.80; P = .01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00–7.43; P = .05), whereas γ11- and γ12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21–46.17; P = .03; and OR, 6.71; 95% CI, 1.47–30.75; P = .01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10–51.04; P = .04 and OR, 5.31; 95% CI, 1.13–24.95; P = .03, respectively). CONCLUSIONS AND RELEVANCE This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

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Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma

Cited by 87 publications

References 27 publications

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Associations of Oral α-, β-, and γ-Human Papillomavirus Types With Risk of Incident Head and Neck Cancer

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