Recurrent Oral Squamous Papilloma in a HIV Infected Patient: Case Report

The Human Papillomavirus (HPV) is a DNA virus of the Papilomaviridae family that cannot be cultivated. It is a small, non-enveloped virus of about 55nm in diameter. It is comprised of 72 capsomers in one capsid of icosahedral symmetry.(1) It presents considerable tropism for epithelial and mucous tissues having a variable incubation period that can last from three weeks to an indeterminate period (2, 3). This virus may be associated to sexual transmission ranging from oral lesions to the formation of cervical cancer, constituting high-impact pathology (4).


Introduction
The Human Papillomavirus (HPV) is a DNA virus of the Papilomaviridae family that cannot be cultivated.It is a small, non-enveloped virus of about 55nm in diameter.It is comprised of 72 capsomers in one capsid of icosahedral symmetry.(1)It presents considerable tropism for epithelial and mucous tissues having a variable incubation period that can last from three weeks to an indeterminate period (2,3).This virus may be associated to sexual transmission ranging from oral lesions to the formation of cervical cancer, constituting high-impact pathology (4).
Various types of HPV has been described, with oncogenic potential and associated to oral lesions: Squamous papilloma (SP), condyloma acuminatum (CA) and focal epithelial hyperplasy (FEH) are the most frequent pathological entities associated to HPV, and this virus has been identified and correlated to the lichen planus (LP), Pemphigus vulgaris (PV), squamous cell carcinoma (SCC) and verrucose carcinoma (VC) (7).Currently oral manifestations of the HPV infection have increased in patients infected with HIV/AIDS, including children patients (8).This report discusses the vulnerability of HIV infected individuals to HPV infection as well as the knowledge required by clinicians.As such, the objective of this study is to relate a case of a HIV-infected patient with a recurrent oral lesion associated to HPV, monitored at the Oral Pathology department of Federal University from Rio de Janeiro (UFRJ), under informed consent of the patient.

Case report
A white male patient, 44 years was referred to the Department of Oral Pathology at Rio de Janeiro Federal University, complaining of swelling on tip of tongue, started seven months earlier.During anamnesis the patient related a history of multiple sexual partners, and practice of unprotected oral, vaginal and anal sex, with previous episodes of sexuallytransmitted diseases (STD) (gonorrhea and syphilis) adequately treated.
The patient reported being HIV-infected for 10 years and no antiretroviral therapy.Blood evaluation showed a CD4 T lymphocyte count of 640 cells/mm³ and viral load of 585 copies/ml.Oral examination revealed a red verrucous 3 mm diameter lesion, on the left side of the tongue, suggestive of oral SP (figure 1).An excisional biopsy was carried out, and postoperative advise given.The histopathology showed morphology compatible with SP (figure 2), and the patient was informed about HPV infection, the risk of relapse, the risk of oral-genital transmission, and the importance of periodic monitoring.Two months after, a further vegetative 2 mm diameter verrucous lesion on the same site was revealed, indicating relapse.A repeat excisional biopsy was taken, and the histopathology indicated SP.At present the patient is under periodic clinical check-up.

Discussion
The high number of different sexual partners, immunologic deficiency and STDs make the incidence of HPV infection increasingly high (2).This infection often occurs on oral mucosa and the sites most involved are labial mucosa, with 55% of cases, the palate, jugal mucosa, gums, tonsils, uvula and roof of the mouth (9).Although the tongue is not commonly affected, the case presented both lesions on the tip of this organ.
One study evaluated clinical and histopathological features in 12 oral lesions of SP -being the tongue -and found that the time development of these lesions ranged from 2 months to 20 years, being the tong the most prevalent site, with lesions about 3 mm in diameter, with rounded appearance (10).SP can be further divided into several types: isolated, solitary and multiple-recurring (11).The findings observed in this study showed that lesion development (about 7 months), in the lingual site as the most frequent and round lesion.
HPV infection can occur in three ways: transitory infection in 50% of cases; spontaneous regress lesions in 30% of cases; and persistent infections, with constant relapses.Clinically the lesions normally have a verrucous aspect that may be not detected by visual inspection, but through magnification techniques such as colposcopy.Diferent laboratory techniques for diagnosis should read as cytology, biopsy, immunohistochemistry and molecular techniques (2,3).
The oral SP is a benign entity presented as an exophytic lesion, with a rugose red or white surface, sessile or pediculed (12).It can be granular, fingerlike and may be asymptomatic.(11).In this case both lesions were clinically considered verrucous, vegetative and sessile.
The classical manifestations of HPV infection is the CA followed by verruca vulgaris (VV) and FEH.However, the virus has been identified in other oral afflictive entities such as VP, LP and leukoplasies, probably representing a coincidence of tissue infection and not a causal factor.
As for its differential diagnosis, the literature shows that other diseases may be an oral challenge to diagnose as condyloma acuminatum, verruca vulgaris, focal epithelial hyperplasia (Heck disease), papillary hyperplasia and verruciformis, because they are among a clinically and/or histopathological the injuries that present similarities although the feature distinct, it needs an sufficient training for the health professional to perform an adequate approach to these lesions (13) Although many oral SP appear to be of viral etiology, the infectivity of the HPV must be of a very low order.The route of transmission of the virus is unknown for oral lesions, although direct contact would be favoured as in the present case.Surgical removal is the treatment of choice by either routine excision or laser ablation.Other treatment modalities include electrocautery, cryosurgery, and intralesional injections of interferon.Recurrence is uncommon, except for lesions in patients infected with human immunodeficiency virus (HIV) (10,11).
HPV related lesions are usual in HIV infected patients, in both genital and oral sites (14).Morphologically, hyperkeratosis, koilocytosis, diskeratosis, papillomatosis and acanthosis, whenever present in papilloma lesions suggest HPV infection (15,16).However, other benign oral lesions such as VV, CA and FEH more readily present cytopathic effects induced by HPV than papilloma (17).Papillomavirus was also found for the first time in endodontic abscesses (18).
A report showed that the prevalence of HPV in HIV-infected adults is greater (36.4%) than in HIV-negative patients (6.1%) (19).However, a study in children, showed a prevalence of 3.6% in HIV+ patients against 12.3% of those not infected (20).Therefore, more studies into HPV infection and prevalence among the HIV+ individuals are needed in order to clarify the significance of these lesions.It seems that an emphasis on HIV treatment rather than on the HIV immunosuppression has had a noticeable role in oral HPV infections in HIV + individuals.(CAMERON 2005).(21) Owing to the oncogenic role of certain types of HPV, the relation between this virus and carcinogenesis in oral mucosa is still controversial.Various studies have identified HPV in biopsies of oral SCC and VC (4,9,12).Among HPV types found in the oral mucosa, types 6 and 11 are more prevalent in benign lesions on the oral epithelium and types 16 and 18 more prevalent in malignant lesions.In this case HPV identification was not done as the material sent for analysis was scarce (4,9).
The methods of HPV identification in human tissue vary in sensitivity include electronic microplasy, immunohistochemistry, immunofluorescence, hybridization in situ, Southern blot, dot blot, reverse blot hybridization and polymerase chain reaction (PCR) (22).Morphological analysis cannot typify the virus, but can suggest its presence, being useful in public health policies (12,23).
The table below shows HPV identification studies as well as the types most frequently found.

HPV types Reference Year
In  1.
The treatment of oral SP may be clinical, by the use of keratolytic agents such as trichloroacetic acid (40 -90%), a podophyllum 25%, 5-fluoracil and imiquimod; or surgical, by cold, electrical or laser excision.Surgical removal is recommended in few lesions presentations and when histopathological analysis is desired (2,3,9).
The patient should be monitored for 6 (six) months after treatment of lesions, which is a critical period for recurrence (2,3).This data is in agreement to the present report, as relapse occurred in the second month of outpatient monitoring.
One study showed that majority of men do not seek medical care or advice when they have advanced symptoms of HPV infection, and especially when it causes some discomfort.The major concern of infected individuals is in the consequences of this infection in terms of their social and sexual lives.Fear and pain are also raising questions present feelings and anxieties, and consequently suffering.The men in general are very dependent on their sexuality and regard penis as the main organ of the body (28,29).
The patient infected by HPV has affected sex life leading to insecurity in all aspects of life, going to be afraid of losing their jobs if discovered, fear of rejection from their partner, fear of betrayal and fear of comment friends (28,29).
A nested case-control study conducted with 2194 HIV-positive patients showed no association between changes in CD4 cell count and risk of oral warts (30).
The main causes of transmission of HPV infection are the lack of prevention information, prejudices, early onset of sexual activity, multiple partners, not using condoms.Health professionals should play a role through educational activities, working with sexual health promotion and prevention information, encouraging protected sex practices, while respecting the socio-cultural needs of each individual and promoting the biopsychosocial help (28,29).At the present moment, there are two types of HPV prophylactics vaccines, a bivalent that protect against HPV-16/18 and the quadrivalent (HPV-6,11,16).These vaccines are available globally.There is no reason to believe that the vaccine don't work against HPV at the oral mucosa or another anatomical site (31,32,33).

Conclusion
Oral lesions may represent an important significance for professionals who treat HPV infection or other STDs.Research into oral cavity lesions should be given value by the dental surgeon or other health professionals who treat HPV infection cases or other STDs.Furthermore, prevention is the most efficient strategy for HPV infection control, including HPV vaccination for oral and genital infection, through suitable sexual guidance in order to reduce situations of vulnerability.

Fig. 1 .
Fig. 1.Verrucose lesion on the left side of the tongue.