Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Herpes Simplex

  • Jacqueline E. van der WalEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_729-1


Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are the two strains of the herpes family, Herpesviridae, which infect man and especially the oral cavity or genitals. Generally, HSV-1 gives rise to infections “above the waist” and HSV-2 “below the waist.” Both types are neurotropic.

Most primary HSV infections are acquired through direct contact with a lesion or with infected body fluids, especially saliva. Asymptomatic shedding occurs principally in the prodrome phase of the primary disease.

Clinically, the oral HSV-1 infection presents as gingivostomatitis. Most primary infections in children are mild to symptomatic, with only 10/20% very mild symptoms and arise after an incubation period of 2–20 days. The oral lesions may be accompanied by pyrexia, lethargy, loss of appetite, hypersalivation, and cervical lymphadenopathy. Due to difficulty in maintaining good oral hygiene, there can be oral malodour and a coated tongue.

HSV-1 has been suggested as a risk factor in the development of human malignancies in association with tobacco and alcohol, including head and neck cancer.

Oral HSV-2 infection can be seen in older patients or as a complication of long-term immunosuppression.

Clinical Features

  • Incidence

    HSV-1 infection occurs worldwide and has no seasonal variation.

    Asymptomatic individuals periodically shed infectious HSV in saliva, observed in 2–9% of cases. Viral shedding is greater in immunocompromised patients or those undergoing oral surgery (38% and 20%, respectively). The prevalence increases from childhood to later adult years (70–80%), being greater in lower socioeconomic groups. Seroprevalences increase up to 90% by the fifth decade of life in some studies.

  • Age

    All ages, from childhood to adulthood. Primary gingivostomatitis has two age/peaks, first during childhood, usually between 6 months and 5 years of age, and secondly in the early 20s.

  • Sex

    No sex predilection.

  • Site

    Symptomatic primary gingivostomatitis affects the tongue, lips, gingivae, buccal mucosa, and hard and soft palate. The lesions are ½ mm vesicles which rapidly turn into small, painful ulcers, covered by a pseudomembrane and surrounded by an erythematous halo (Fig. 1).

  • Treatment

    The ulcers heal within 10/14 days without scarring. Specific antiviral therapy in an otherwise healthy individual is rarely necessary. Symptomatic treatment or local antiviral agents can give some relief. Significant acceleration in clinical resolution can be seen when acyclovir suspension is initiated during the first 3 symptomatic days.

  • Outcome

    Recurrent herpetic infection, also known as herpes labialis, is due to a reactivation of the virus in the secondary ganglion. It can be spontaneous or triggered by factors as fever, UV-light exposure, common cold, emotional stress, immunosuppression, viral infections, etc. The recurrences occur at variable intervals, ranging from months to years. Secondary infections occur in 20–40% of HSV-1 seropositive persons. The lesions occur on the mucocutaneous junction of the face, usually on the lips. These lesions start as red macules, changing into highly infective vesicles with finally pustular scabs and ulcers. These lesions heal within 1–10 days of the onset of the initial symptoms.

    These recurrences can also occur in the oral mucosa, known as recurrent herpetic stomatitis. The lesions occur on the keratinized mucosa, in contrast with recurrent aphthous stomatitis which occurs on the nonkeratinized mucosa. The lesions are typically few in number (<4), small (<1 cm), mildly painful, and last <10 days.
    Fig. 1

    HSV-infection on the gingiva (Courtesy of Prof. Dr. A. Vissink, Department of Oral & Maxillofacial Surgery, UMCG, Groningen, the Netherlands)


Microscopically, the squamous epithelium shows acantholysis with floating of individual acantholytic cells in the vesicle or ulcer (Tzanck cells), nuclear clearing, and enlargement (ballooning degeneration) with nucleolar fragmentation with condensation of chromatin around the nucleus. Multinucleated cells are present as a result of fusion of between adjacent cells. Due to secondary ulceration, an inflammatory infiltrate may be present in the underlying connective tissue (Figs. 2 and 3).
Fig. 2

Low power view with acantholysis with ballooning degeneration of cells (H&E)

Fig. 3

Detail of Fig. 2 with ground-glass appearance of the nuclei and multinucleation (H&E)


In case of doubt an immunohistochemical staining for HSV can be performed.

Molecular Features

Detection of HSV-1 by viral isolation in tissue culture systems in case of atypical presentation of the infection. However, polymerase chain reaction (PCR) is more sensitive for the detection of HSV.

Differential Diagnosis

Recurrent herpetic stomatitis occurs on the keratinized mucosa, in contrast with recurrent aphthous stomatitis which occurs on the nonkeratinized mucosa.

References and Further Reading

  1. Arduino, P. G., & Porter, S. R. (2006). Oral and perioral herpes simplex virus type I (HSV-1) infection: Review of its management. Oral Diseases, 12, 254–270.CrossRefPubMedGoogle Scholar
  2. Arduino, P. G., & Porter, S. R. (2008). Herpes simplex virus type I infection: Overview on relevant clinico-pathological features. Journal of Oral Pathology & Medicine, 37, 107–121.CrossRefGoogle Scholar
  3. Elad, S., Zadik, Y., Hewson, I., Hovan, A., Correa, M. E. P., Logan, R., Elting, L. S., et al. (2010). A systematic review of viral infections associated with oral involvement in cancer patients: A spotlight on Herpesviridae. Supportive Care in Cancer, 18, 993–1006.CrossRefPubMedGoogle Scholar
  4. Jain, M. (2016). Assessment of correlation of herpes simplex virus- with oral cancer and precancer – A comparative study. Journal of Clinical and Diagnostic Research, 10, ZC14–ZC17.Google Scholar
  5. Kolokotronis, A., & Doumas, S. (2006). Herpes simplex virus infection, with particular reference to the progression and complication of herpetic gingivostomatitis. Clinical Microbiology and Infection, 12, 202–211.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PathologyAntoni van Leeuwenhoek Hospital/The Netherlands Cancer InstituteAmsterdamThe Netherlands