Condyloma acuminatum An Opportunistic Infection Found in the Oral Cavity

Tools



Abstract

In the Department of Oral and Maxillofacial Surgery, a 42 year old male presented with an overt manifestation of oral human papillomavirus, a case of condyloma acuminatum. The patient was treated with excisional biopsy with heighted concern for a cosmetic result and potential for premalignacy.

Introduction

The prevalence of human papillomavirus (HPV)-associated oral condyloma has reportedly increased in HIV- infected individuals since the introduction of (HAART). 1   In the oral cavity, care must be taken to differentiate between squamous papilloma, condyloma acuminatum, and verruca vulgaris.  Clinical and pathologic correlation is often required. We report on a patient who had a complex of symptoms which was diagnosed as oral condyloma acuminatum.

Case Report

A 42-year-old African American male presented to Howard University Hospital (HUH) Oral and Maxillofacial Surgery Clinic, complaining of pain in the right side of his mouth. Patient was referred from HUH Cares, which provides services for families living with HIV/AIDS, for evaluation of papillary lesions and extraction of all remaining teeth in preparation for complete dentures. The patient’s chief complaint was a sore in the right side of his mouth for one month and he was concerned about multiple small bumps inside his mouth. The medical history included hypertension, HIV infection, and gout.

During physical examination, the extra oral examination was positive for multiple small, soft, pink papillomatous nodules on the skin of the right upper lip and right commissure, without tenderness.

(Fig. 1 A, B)
(Fig. 1 A, B)

The lip lesions crossed the wet lip line to the mucosa. There were two extraoral clusters of pink, dusky gray, pedunculated papillary nodules in the right commissure that measured approximately 1.8 x 1.7 cm in aggregate and an upper lip lesion left of midline, approximately 1 x 1cm in greatest dimension. The borders were raised and rounded, with a pebbly texture, and the surface was focally ulcerated.

(Fig. 2 A, B)
(Fig. 2 A, B)

The intraoral lesions were multiple pinkish-white, soft, cauliflower-like nodules, approximately 2 cm in diameter, with broad finger-like projections, irregular borders and a rough texture. The overlying skin and mucosa did not exhibit any altered sensation.

The intraoral exam showed poor oral hygiene, multiple carious anterior teeth, and an edentulous posterior maxilla and mandible. There was no ulceration, no discharge, no floor of mouth elevation, and no dysphagia. No palpable lymph nodes were detected.

Radiographic examination revealed a partially edentulous maxilla and mandible with normal bone trabeculation, pneumatized sinuses and no intrabony pathology other than multiple periapical radiolucencies.

Differential Diagnosis

Differential diagnosis for the multiple papillary nodules on gingival and mucosal tissue included condyloma acuminatum, squamous papilloma, and verruca vulgaris. All the considerations involve human papilloma virus (HPV).

HPV comprises a large family of double stranded DNA viruses that are the etiologic agents of diseases as diverse as benign warts and anogenital cancers. HPV is difficult to grow in vitro; however, in vivo, once an individual becomes infected with HPV, it can be difficult or even impossible to eradicate. 2

Condyloma acuminatum is a common, sexually transmitted disease associated with HPV-6 and HPV-11, although high risk types 16 and 18 may be present, especially in anogenetal lesions.  In addition, lesions may be spread through autoinnoculation.  Condyloma acuminatum is a benign lesion with varied color typically found in anogenital and oral region. 3  Lesions are often clustered in groups and typically are 1.0 to 1.5 cm in diameter.  Some authors describe the soft, exophytic, papillomatous growths with a sessile or pedunculated base. 4   Microscopically, the viral cytopathologic effect is seen as koilocytosis, small, wrinkled nuclei with perinuclear halos.  Koilocytes are typically observed in the superficial epithelial cells and may be considered a hallmark of HPV infection.

Excisional biopsy is indicated for lesions that are atypical, recurrent after initial success of removal, or resistant to treatment or in patients who are immunosuppressed or with a high risk for neoplasia. The location and extent of the lesion and the potential for malignant transformation largely dictate treatment.

Squamous papilloma is a common, intraoral, benign epithelial growth seen in adults. Most of these lesions are believed to be associated with HPV- 6 and HPV- 11. 5  Squamous papilloma is most frequently found in the posterior hard palate, soft palate and uvula (34%), dorsum and lateral tongue borders (24%), gingiva (12%), lower lip (12%), buccal mucosa (6%). 5  Clinically, the white-pink cauliflower-like surface projections are usually less than 1 cm in size.  Microscopically, they are finger like projections with delicate fibrovascular cores surrounded by benign squamous epithelium. Lesions may have mildly atypical mitotic figures in variable hyperplasia of the basilar level, and often demonstrate no koilocytotic changes in the superficial epithelium. 5  There is a low recurrence rate. Papillomas are not contagious, unlike a wart, and therefore can be removed by conservative surgery or laser ablation.

Common cutaneous warts, or verruca vulgaris, generally appear on keratinized skin, presumably at the site of inoculation, and may also be seen on the mucosa. Lesions may spread through autoinoculation, similarly to condyloma acuminatum. HPV is believed to cause the common wart or verruca vulgaris. Verruca vulgaris of the oral mucosa is typically seen in childhood, but occasionally adults may be affected. 6  Clinically, warts appear as circumscribed, sessile, rough, papules or nodules. Skin lesions develop most often on the hands, fingers, feet, and knees. 7  When oral mucosa is involved, the lesion is typically found on the vermilion border, labial mucosa, or anterior tongue. 6  Histologically, common warts demonstrate hyperkeratosis, acanthosis, parakeratosis, and papillomatosis. Uncomplicated lesions can be treated with chemical ablation, cryoablation, surgical excision, or laser treatment. Because the virus is present in the basal layer of the epidermis in a latent state and because autoinoculation may occur, recurrences are common and retreatment may be necessary. 8

Diagnosis

We chose the extraoral lesion to biopsy initially. A wedge excision with primary closure was performed.

(Fig. 3 A, B) The lesion was less than 1/3rd of the lip and orienting the incision in the relaxed skin tension lines minimized the appearance of the scar. The excised specimen was approximately 3 x 1.4 x 0.5 cm.
(Fig. 3 A, B) The lesion was less than 1/3rd of the lip and orienting the incision in the relaxed skin tension lines minimized the appearance of the scar. The excised specimen was approximately 3 x 1.4 x 0.5 cm.
Fig. 4 All redundant tissue was excised to prevent puckering of the incision.
Fig. 4
All redundant tissue was excised to prevent puckering of the incision.

Fig. 5
The surgeon closed the epidermis with careful approximation of the incision, taking care to evert the wound edges to prevent a depressed and noticeable scar.

The histopathologic examination of the specimen, reviewed by the Pathology Department, revealed papillary projections, surfaced by orthokeratotic squamous epithelium and each projection was supported by a delicate fibrovascular core. The histologic findings were consistent with the clinical consideration of condyloma acuminatum. No epithelial dysplasia was identified.

(Fig. 6 A, B) Low power magnification of hematoxylin and eosin stain (A), High power magnification of hematoxylin and eosin stain (B).
(Fig. 6 A, B) Low power magnification of hematoxylin and eosin stain (A), High power magnification of hematoxylin and eosin stain (B).

Discussion

Papillomatous lesions are not an uncommon finding in the oral cavity of patients infected with HIV. Furthermore, HIV patients also have higher rates of treatment failure and more rapid neoplastic progression and recurrence of anogenital and oral HPV infection. 9  Distinguishing condyloma acuminatum from verruca vulgaris or squamous papilloma may require clinical and pathologic correlation. Three microscopic features are helpful to distinguish warts from other papillomatous lesion, to include the presence of koilocytes, vertical columns of parakeratosis, and foci of clumped keratohyaline granules; none of these features were present in this case. The large clinical size of the lesion also favored condyloma over verruca or papilloma. The patients did not have lesions of the hands, also not in favor of verruca vulgaris. Clinicians must be sensitive to the social implications of diagnosing condyloma. In this case, following the diagnosis of these oral lesions, the Sexually Transmitted Disease clinic confirmed that the patient had penile lesions of condyloma.

The progression of HPV lesions, from benign hyperplasia to carcinoma in situ, is affected by additional factors, including host immune response. 10  HIV status directly affects immune status, which modulates susceptibility to opportunistic infections, including HPV. Additionally, development of HPV tumors may be affected by HIV status, since surveillance of tumor cells is impaired. It is well established that additional cofactors, such as alcohol, drugs, smoking, oral contraceptives, and hormone levels may influence HPV infection and progression of HPV-induced cancers, particularly anogenital lesions. 10

In the era of HAART, the survival rate of the HIV- infected individuals has increased dramatically, mainly due to the suppression of HIV viral load and the restoration of the immune response. In addition to the increased incidence of HPV related lesions in patients on HAART, AIDS associated cancers may continue to be of major clinical interest. Identification of an association between viruses and various types of cancer is important in that it opens up new possibilities for cancer prevention and treatment. This area provides continued interest because the complete mechanisms by which malignancies arise in infected individuals is not exactly known. 10  The importance of clearly identifying the mechanism linking viruses and various types of cancer may lead to new treatments. With these various strategies, the worldwide incidence of virus-associated cancers may be reduced.

Fig 7A

Fig. 7 A, B Final result after uneventful healing, week 1 and week 2
Fig. 7 A, B Final result after uneventful healing, week 1 and week 2

References

  1. Shetty K, Leight J. The Role of Human Papillomaviru (HPV) and The Increasing Incidence Of Oral Pathology In The Era Of Highly Active Antiretroviral Therapy (HAART).Int Jou Dent Sci. 2005;2. Available at http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijds/vol2n2/hpv.xml. Accessed December 19, 2007.

  2. Carr J, Gyorfi T. Human papillomavirus. Epidemiology, transmission, and pathogenesis. Clin Lab Med. 2000;20:235-55.

  3. Felefli S, Flaitz CM. Oral warts in HIV-infected individuals. RESEARCH INITIATIVE/TREATMENT ACTION! Sept 2000. Available at http://www.accessmylibrary.com/coms2/summary_0286-28425886_ITM Published September 1, 2000. Accessed October 11, 2007.

  4. Green TL, Eversole LR, Leider AS. Oral and labial verruca vulgaris: clinical, histological, and immunohistochemical evaluation. Oral Surg Oral Med Oral Pathol. 1986;62:410-416.

  5. PathologyOutlines.com, Inc, Oral cavity and Oropharynx, Last revised 17 April 2008, Last major update June 2004,Copyright (c) 2004-2008. Available at http://www.pathologyoutlines.com/oralcavity.html Accessed October 11, 2007.

  6. Abbey LM, Page DG, Sawyer DR. et al. The clinical and histopathologic features of a series of 464 oral squamous cell papillomas. Oral Surg Oral Med Oral Pathol. 1980;49:419-428.

  7. Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis.2002;35:S210-24.

  8. Fazel N, Wilczynski S, Lowe L, Su LD. Clinical, histopathologic, and molecular aspects of cutaneous human papillomavirus infections. Dermatol Clin.1999;17:521-36.

  9. Unger ER, Vernon SD, Lee DR,et al. Human papillomavirus type in anal epithelial lesions is influenced by human immunodeficiency virus. Arch Pathol Lab Med. 1997; 121:820-4.

  10. Angeletti PC, Zhang L, Wood C. The Viral Etiology of AIDS-Associated Malignancies.Adv Pharmacol. 2008; 56:509-557.