Elsevier

Human Pathology

Volume 53, July 2016, Pages 130-136
Human Pathology

Original contribution
Prevalence and distribution of 15 high-risk human papillomavirus types in squamous cell carcinoma of the scrotum☆,☆☆

https://doi.org/10.1016/j.humpath.2016.02.013Get rights and content

Summary

Which subtype(s) of high-risk human papillomavirus (hrHPV) are involved in squamous cell carcinoma (SCC) of the scrotum is unknown. Twenty-seven cases of SCC of the scrotum were retrieved, and all 15 subtypes of hrHPV and their viral loads were assessed using multiplex real-time polymerase chain reaction. The results were correlated with the histopathologic features, p16 expression, and in situ hybridization for hrHPV. hrHPV was identified in 18 (67%) of 27 of the cases, including HPV16 (n = 8), HPV35 (n = 7), HPV31 (n = 5), HPV59 (n = 5), HPV33 (n = 3), HPV18 (n = 2), HPV51 (n = 2), HPV39 (n = 1), HPV56 (n = 1), and HPV82 (n = 1). Of the 18 cases, 10 (56%) were infected by multiple hrHPV subtypes. In situ carcinomas had higher viral loads than invasive (50 M versus 2 M in average). The average age of HPV-positive and -negative cases was similar, 55 and 51, respectively. Of 11 cases of invasive carcinoma, 5 (45%) were positive for hrHPV versus 13 of 16 (81%) of in situ carcinomas. The highest proportion of hrHPV-positive cases was seen in basaloid type (7/7; 100%) and warty type (4/4; 100%), followed by usual type (7/16; 44%). Of 18 of the HPV-positive cases, 9 (50%) were also positive for p16 by immunohistochemistry and 6 of 18 (33%) were positive by in situ hybridization. Similar to SCC of the vulva and penis, the most frequently HPV-positive tumors are basaloid and warty types. However, a proportion of SCC usual type are also positive for hrHPV. Our results show that 8 (44%) of 18 of cases are associated with hrHPV subtypes other than 16 and 18. Additionally, 7 (70%) of 10 of hrHPV16/18-positive cases are coinfected with other subtypes.

Introduction

High-risk human papillomavirus (hrHPV) is involved in carcinogenesis of multiple organ sites including uterine cervix [1], vagina and vulva [2], anus [3], penis [4], and oropharynx [5]. Previously, we reported a contemporary series of squamous cell carcinoma (SCC) of the scrotum where we identified 7 of 29 cases that were positive for hrHPV [6]. However, the specific subtype(s) of hrHPV that was involved in each case was unknown because in situ hybridization technique with a cocktail of biotinylated probes against multiple genotypes was used. With the introduction of the HPV vaccine, identification of the hrHPV genotype has become important not only to understand the mechanisms involved in malignant transformation but also for practical/clinical purposes to evaluate the potential coverage of the currently available HPV vaccines. To identify which genotypes are involved in squamous neoplasia of the scrotum, we performed multiplex real-time polymerase chain reaction–based study to all 15 types of hrHPV considered to be involved in human cancer. We correlated the results with the histopathologic features, immunohistochemistry (IHC) for p16, and in situ hybridization for hrHPV.

Section snippets

Study population

The Internal Review Board of Rhode Island Hospital approved this study. Twenty-seven patients with in situ or invasive SCC of the scrotum from which there was sufficient material to perform the testing were included. We included deidentified cases from our previously published series on SCC of the scrotum [6]. Hematoxylin and eosin–stained slides were reviewed in each case by A. M. and J. I. E., and the cases were classified based on the morphologic features into basaloid, usual, and warty

Results

A summary of the morphologic classification of cases and the results of the hrHPV studies is presented in Table 1. Most cases were morphologically classified as usual type (n = 16; 59%), defined by the presence of keratinization. Absence of morphologic evidence of keratinization (pearls or cytoplasmic eosinophilia) is sufficient to exclude a tumor from this category (Fig. A and B). Of the 16 cases of usual type, 8 (50%) were invasive. Three cases were positive for p16 (18%) by IHC, and only 1 was

Discussion

hrHPV has been previously associated to SCC of the scrotum [9], [10], [6]. In this study, we tested all the hrHPV genotypes most commonly associated with human cancer [11], [12], [13], [1]. Identification of the hrHPV genotypes involved in oncogenesis in different sites has practical implications after the introduction of the HPV vaccines to prevent cervical cancer. Although HPV vaccination has the potential to reduce the incidence of cervical cancer, the incidence of other HPV-associated

Conclusions

We report the prevalence and distribution of all 15 hrHPV genotypes involved in SCC of the scrotum. We have identified a significant proportion of cases that are hrHPV associated, including many cases of usual type SCC. Additionally, the spectrum of hrHPV subtypes identified is wider than those covered by the currently available vaccines. The clinical significance of the presence of unusual subtypes or simultaneous infection by multiple genotypes is unknown and requires further studies.

Acknowledgments

The authors thank Donfang Yang for her help in the isolation of the DNA.

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    ☆

    Competing interests: Pradip Manna worked for Physician Reference Laboratory. All other authors declare no conflict of interest.

    ☆☆

    Funding/Support: This work was partially supported by the Department of Pathology and Laboratory Medicine of Lifespan Academic Medical Center.

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