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A surprising evolution from oral human papillomavirus 16 infection to lymph node metastasis of tonsilar squamous cell carcinoma in an HIV-infected patient

2012; Lippincott Williams & Wilkins; Volume: 26; Issue: 8 Linguagem: Inglês

10.1097/qad.0b013e3283533b09

1473-5571

Guillem Sirera, Sebastián Videla, M. Paz Cañadas, Laila Darwich, Emanuela D’Angelo, Bonaventura Clotet,

Viral-associated cancers and disorders

Mucosal high-risk human papillomavirus (HPV) types are found in nearly 25% of head and neck cancers (HNCs), and the most common high-risk HPV is type 16. It is found in 90–95% of HPV-positive HNCs [1–3]. On the basis of the knowledge gained from the cervix, more than a decade can pass from HPV-infection to cancer even in HIV-infected patients [4]. However, despite the recognition of the HPV-associated oral malignancy, little is known about the evolution of oral HPV infection to cancer and about the role of HPV in the metastases. To our knowledge, our case illustrates the first report of an HIV-infected patient (63 years old) in which a short period elapsed from HPV-16 detection in the oral cavity to metastatic lesion from HPV-16-related tonsil squamous cell carcinoma. In 1993, HIV infection was diagnosed with an analytical control per patient request (45 years old). The medical history is unremarkable. In 1994, the patient had a CD4 nadir of 34 cells/μl and from 1997 up to now had good highly-active antiretroviral therapy (HAART) adherence (HIV undetectable and CD4 cell count above 500 cells/μl). No opportunistic disease has been diagnosed; only to note that she was a nonsmoker and did not consume alcohol. In March 2008, she was included in the CARH·DONA cohort. This cohort is a prospective, single center of adult HIV-infected female outpatients who are annually assessed for HPV infection in the anus, cervix and mouth. The aforementioned woman was undetectable for oral HPV infection in 2008, 2009 and 2010, but HPV-16 was detected in February 2011. Visual inspection of oral cavity was normal. Oral samples were obtained by brushing with a cytobrush on both sides of the oral cavity and by vigorously swishing and gargling 5 ml of PBS for 30 s and spitting it into a collection recipient (oral rinse). HPV detection and typing were performed using the commercial IVD-CE Multiplex Fluorescent-PCR Kit for HPV Genotyping (F-HPV typing, MolgentixSL, Barcelona, Spain), in accordance with the manufacturer's instructions. In September 2011, she presented with a 4-month history of a cervical lymph node. PET showed a hypermetabolic adenopathy. A metastasis of a squamous cell carcinoma was diagnosed in a biopsy of adenopathy, and the biopsy from tonsil ipsilateral subsequently confirmed the diagnosis: poorly differentiated squamous cell carcinoma (28 September). HPV-16 was integrated in both biopsies (tonsil and adenopathy). Moreover, HPV-16 was detected in a new oral rinse sample, but was undetectable in plasma. It is worth noting that the short period had elapsed from HPV-16 detection in the oral cavity to cancer diagnosis. Assuming that the patient was infected the day after the last negative control for HPV infection in the oral cavity (March 2010) until she noticed the adenopathy (April 2011), hardly a year had passed. This must be seen as a rapid evolution from infection to cancer when compared to the natural history of an HPV-infected cervix. A fast evolution from infection to cancer has to be considered, if it is compared with the natural history of cervix HPV infection. What must be highlighted is that our patient was on HAART, had immunity above 500 CD4/μl and undetectable for HIV. From this case, several issues arise. Is the natural history of HPV-related HNC different than HPV-related cancer of the cervix in HIV-infected patients? Were the assessments of the oral HPV infection prior to 2011 false negative? Detection of HPV infection by molecular techniques such as PCR are the methodology used to study the efficacy of vaccines, for example; and the oral rinse provides the best method for HPV detection in the oral cavity [5]. Is oral sex the main path for the transmission of the infection? Oral HPV infection is related to sexual behavior [6]. Our patient was widowed in 1996. In an ad-hoc interview, she denied the sex practice since becoming a widow. (Might she be lying?). Which risk factors might explain this fast evolution? Being a smoker and alcohol consumer does not seem to be implied in this case. However, the role of integration is unknown. Albeit the normal host immunity may block metastatic disease from HPV-associated head and neck squamous cell carcinoma [7], this case leads us to think that the fast evolution from infection to cancer may be related to HIV infection itself in spite of good HAART adherence and efficacy. In fact, HIV-infected patients presented histological differences in this kind of cancer compared with HIV-uninfected patients [8]. The HIV-infected patients might be expressing a different molecular mechanism in this process. Well designed studies are needed to answer this question. As a physician to HIV-infected patients, the careful inspection of the oral cavity should be routine in each control visit. The patients signed the informed consents to be included in the CARH·DONA cohort and to authorize this case report. Acknowledgements G.S. and B.C. looked after the patient. M.P.C. and L.D. performed detection, genotyping and integration of HPV. E.A. performed the pathological diagnostic from adenopathy and tonsil. S.V., G.S. and B.C. wrote the report. Written consent to publish was obtained. Conflicts of interest S.V. has received honoraria for collaborating with Laboratorios Dr Esteve. B. Clotet has received honoraria for speaking and participating in advisory boards from Abbott, Bristol-Myers Squibb, Boehringer-Ingelheim, Gilead Sciences, GlaxoSmithKline, Pfizer.