Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)

Does hydrochlorothiazide increase the incidence of skin, lip and oral cancer in a UK population?

Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between hydrochlorothiazide (HCTZ) exposure and skin, lip and oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped: squamous cell carcinoma (SCC) skin cancer; basal cell carcinoma (BCC) skin cancer; melanoma; lip cancer and oral cancer. Patients within the lip cancer and oral cancer groups were accepted with a history of non-melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of cancer. Patients with a history of organ transplantation, human immunodeficiency virus (HIV) or immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC, melanoma, lip cancer and oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year HCTZ exposure lag-time and a five-year HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative HCTZ exposure, the number of patients needed to treat to cause one additional cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and lip cancer was significantly elevated with every use of HCTZ. Relative incidence of melanoma and oral cancer was not significantly elevated with HCTZ exposure. Smoking was inversely associated with BCC and melanoma risk, but significantly increased the risk of lip and oral cavity cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC melanoma and oral cavity cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and lip cancer in a UK population is increased with cumulative high-dose HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.

Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.

PURPOSE: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. METHODOLOGY: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). RESULTS: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. CONCLUSIONS: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Association between hydrochlorothiazide exposure and different incident skin, lip and oral cavity cancers: A series of population-based nested case-control studies.

AIMS: Hydrochlorothiazide-induced photosensitivity may increase squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and lip cancer risk. The aim was to quantify these risks. METHODS: Nested case-control studies using data from the UK THIN database from 01 January 1999 to 01 May 2016. Adults with incident SCC, BCC, melanoma, lip cancer and oral cancer were matched (on age, sex and calendar year of cohort entry) to controls using incidence density sampling. Incidence rate ratios (IRR) for each outcome were calculated for ever and cumulative hydrochlorothiazide exposure, measuring the impact of additionally adjusting for smoking and body mass index (BMI). Adjusted rate differences were estimated, including the number needed to harm. RESULTS: Cumulative hydrochlorothiazide doses ≥50 000 mg were associated with a significantly increased risk of SCC IRR = 3.05 (1.93-4.81) and BCC IRR = 1.34 (1.06-1.69). Using a 5-year lag-period, hydrochlorothiazide exposure was also associated with a significantly increased risk of lip cancer (IRR 2.85, 95% confidence interval 1.32-6.15). No significantly increased risk of melanoma or oral cavity cancer was observed. Following adjustment for smoking and BMI, which had inverse associations with several skin cancer types, associations for hydrochlorothiazide remained significant. The overall number needed to harm with high-dose cumulative hydrochlorothiazide exposure was: 804 for SCC; 2463 for BCC, and 200 000 for lip cancer but varied by age and sex. CONCLUSION: Hydrochlorothiazide exposure was associated with an increased risk of SCC, BCC and lip cancer that is not explained following adjustment for smoking and BMI. These findings may support clinical and regulatory decision making.

Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study.

BACKGROUND: The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. METHODS: By using Taiwan's National Health Insurance Research Database (NHIRD), we conducted three separate case-control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008-2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. RESULTS: Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09-7.81) for lip cancer, 1.16 (95% CI 0.98-1.37) for non-lip NMSC and 1.07 (95% CI 0.65-1.76) for melanoma. There was some evidence of a dose-response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82-3.33) for 100,000-149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. CONCLUSION: Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.

Hydrochlorothiazide use is strongly associated with risk of lip cancer.

BACKGROUND: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. OBJECTIVES: To study the association between use of hydrochlorothiazide and squamous cell carcinoma of the lip. METHODS: We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined potential confounders obtained from demographic, prescription and patient registries. RESULTS: Ever-use of hydrochlorothiazide was associated with an adjusted OR for SCC lip cancer of 2.1 (95% confidence interval (CI): 1.7-2.6), increasing to 3.9 (95%CI: 3.0-4.9) for high use (≥25 000 mg). There was a clear dose-response effect (P < 0.001), with the highest cumulative dose category of hydrochlorothiazide (≥100 000 mg) presenting an OR of 7.7 (95%CI: 5.7-10.5). No association with lip cancer was seen with use of other diuretics or nondiuretic antihypertensives. Assuming causality, we estimated that 11% of the SCC lip cancer cases could be attributed to hydrochlorothiazide use. CONCLUSIONS: Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer.

Antihypertensive drugs and lip cancer in non-Hispanic whites.

BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs. METHODS: In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the ß-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking. RESULTS: At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08). CONCLUSION: These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.

Lip nodules caused by hyaluronic acid filler injection: report of three cases.

Many dermal fillers have been used for reducing facial skin lines and for providing lip augmentation, and hyaluronic acid (HA) is one of the most widely used agents. One of the main commercial forms of HA is Restylane (Q Med, Sweden) produced by microbiological engineering techniques. Although HA is non-immunogenic, hypersensitivity and Granulomatous foreign body reactions have been reported. Herein, we report three female patients (average age 56 years) who presented with firm nodular lesions of the lip and a history of injection with HA (Restylane, Q Med, Sweden). Histopathologically, all cases showed pools of amorphous hematoxyphilic material surrounded by bands of densely collagenized connective tissue with no inflammation or foreign body reaction. Histochemical stains confirmed the presence of acid mucopolysaccharides such as hyaluronic acid. We conclude HA (Restylane, Q Med, Sweden) is an inert filler that may persist at an injection site, resulting in a tumor-like nodule.

Labial adenocarcinoma after treatment with cyclosporin a in a patient with panuveitis.

PURPOSE: To report a case of labial basal cell adenocarcinoma in a patient with uveitis on treatment with cyclosporin A. METHOD: Case report. A 73-year-old woman with panuveitis and retinal vasculitis presented with a lump on her lip after 52 months of treatment with cyclosporin A. RESULT: Excision biopsy showed a labial adenocarcinoma. CONCLUSION: Malignancy can occur after long-term cyclosporin A treatment for uveitis.

Promoting effect of snuff in rats initiated by 4-nitroquinoline-N-oxide or 7,12-dimethylbenz(a)anthracene.

A canal was surgically created in the lower lip of male Sprague-Dawley rats and used as a reservoir for moist snuff. A total of 230 animals were randomized into six groups, five containing 40 rats and one containing 30 rats. After 2 wk of recuperation, the animals were treated as follows. Group I was initiated with 7,12-dimethylbenz(a)anthracene 3 times/wk for 4 wk followed by cotton pellet administration. Group II was initiated with 7,12-dimethylbenz(a)anthracene for 4 wk followed by snuff twice a day, 5 days/wk. Group III received snuff twice a day, 5 days/wk. Groups IV and V were initiated with 4-nitroquinoline N-oxide 3 days/wk for 4 wk. Thereafter Group IV received a cotton pellet, and Group V rats were treated with snuff twice a day, 5 days/wk. Group VI received a cotton pellet once a day, 5 days/wk. Treatment of all groups continued for a maximum of 104 wk. Group V rats had a significantly lower mean survival time than did the other groups because of the development of lip sarcomas in 66% of the rats as compared with 23% in Group II and 26% in Group III. One rat in each of Groups IV and VI developed lip sarcomas. The incidence of sarcomas in Group V as compared with the other groups is statistically significant (P less than 0.05 to 0.001). Spindle cell proliferation, a possible precursor lesion of lip sarcoma, was found in five rats of Group II, seven of Group III, and four of Group V. These results show that snuff has strong promoting capability with regard to the development of lip sarcomas after 4-nitroquinoline N-oxide initiation, but not after 7,12-dimethylbenz(a)anthracene initiation. Snuff by itself caused three squamous carcinomas of the palate, two squamous cell papillomas of the lip, and ten lip sarcomas (in 38 rats as compared with one lip sarcoma in 30 control rats), showing snuff to be carcinogenic for the lip and oral cavity.

Efectos tumorigénicos del condensado de humo de cigarros sobre la mucosa labial de ratones IBFI / Tuorigenic effects of cigarette smoke condensate on the labial mucosa of IBFI mice

Con el objetivo de precisar las alteraciones morfológicas producidas por la aplicación de un condensado de humo de cigarrillos sobre la mucosa labial y su relación con el tiempo de aplicación del carcinógeno, se seleccionaron 120 ratones IBFI entre 4 y 6 semanas de nacido. Los animales recibieron alimento y agua ad libitum y fueron divididos en 4 grupos. Dos grupos fueron tratados con carcinógenos, unos de ellos con el benzo (a) pireno y el otro con un condensado de humo de cigarrillos negros. Un tercer grupo fue tratado con acetona y quedó un grupo no tratado como control. Durante 44 semanas se aplicaron 10 *L de las sustancias empleadas en la mucosa labial de los animales 3 veces a la semana. Todos los animales fueron autopsiados y se realizó disección de labio y lengua. En la semana 44 se presentaron carcinoma epidermoides evidentes tanto en los grupos que recibieron benzo (a) pireno como condensado de humo. Las modificaciones hísticas, más relevantes en diferentes etapas fueron la queratinización superficial, el grosor epitelial y la displasia previas a los estadios neoplásticos

Efectos tumorigénicos del condensado de humo de cigarros sobre la mucosa labial de ratones IBFI / Tumorigenic effects of cigarette smoke condensate on the labial mucosa of IBFI mice

Con el objetivo de precisar las alteraciones morfológicas producidas por la aplicación de un condensado de humo de cigarrillos sobre la mucosa labial y su relación con el tiempo de aplicación del carcinógeno, se seleccionaron 120 ratones IBFI entre 4 y 6 semanas de nacido. Los animales recibieron alimento y agua ad libitum y fueron divididos en 4 grupos. Dos grupos fueron tratados con carcinógenos, unos de ellos con el benzo (a) pireno y el otro con un condensado de humo de cigarrillos negros. Un tercer grupo fue tratado con acetona y quedó un grupo no tratado como control. Durante 44 semanas se aplicaron 10 *L de las sustancias empleadas en la mucosa labial de los animales 3 veces a la semana. Todos los animales fueron autopsiados y se realizó disección de labio y lengua. En la semana 44 se presentaron carcinoma epidermoides evidentes tanto en los grupos que recibieron benzo (a) pireno como condensado de humo. Las modificaciones hísticas, más relevantes en diferentes etapas fueron la queratinización superficial, el grosor epitelial y la displasia previas a los estadios neoplásticos

Empleo de la quimioterapia experimental en la caracterización biológica de un carcinoma epidermoide / Use of experimental chemotherapy in the biological characterization of an epidermoid carcinoma

Con el objetivo de identificar la respuesta de un carcinoma epidermoide, quimioinducido en el labio de ratones IBF1 (IOR/Hab x C57BL/6 Hab) mediante aplicaciones tópicas de un condensado de humo de cigarros, ante la quimioterapi oncológica, se les trasplantó dicho tumor a 52 hembras de 4 a 6 semanas de vida y de 20 a 22 gramos de peso corporal. Las drogas empleadas fueron ciclofosfamida (25 mg/kg; metotrexate (1 mg/kg); bleomicin (2 mg/kg); cisdíamino dicloro platino II (1 mg/kg); administradas por vía intraperitoneal durante 5 días consecutivos una vez transcurridas 48 horas del trasplante. La evaluación antineoplásica se realizó sobre la base de la supervivencia y por las medidas del volumen tumoral durante la evaluación del experimento una vez concluidos los tratamiento antitumorales. Entre los 7 y 12 primeros días de evolución después de concluido el ciclo de tratamiento de los diferentes citostáticos el crecimiento volumétrico resultó lento en relación con los controles, y no rebasó en este periódo 0,7 cm3

Empleo de la quimioterapia experimental en la caracterización biológica de un carcinoma epidermoide / Use of experimental chemotherapy in the biological characterization of an epidermoid carcinoma

Con el objetivo de identificar la respuesta de un carcinoma epidermoide, quimioinducido en el labio de ratones IBF1 (IOR/Hab x C57BL/6 Hab) mediante aplicaciones tópicas de un condensado de humo de cigarros, ante la quimioterapi oncológica, se les trasplantó dicho tumor a 52 hembras de 4 a 6 semanas de vida y de 20 a 22 gramos de peso corporal. Las drogas empleadas fueron ciclofosfamida (25 mg/kg; metotrexate (1 mg/kg); bleomicin (2 mg/kg); cisdíamino dicloro platino II (1 mg/kg); administradas por vía intraperitoneal durante 5 días consecutivos una vez transcurridas 48 horas del trasplante. La evaluación antineoplásica se realizó sobre la base de la supervivencia y por las medidas del volumen tumoral durante la evaluación del experimento una vez concluidos los tratamiento antitumorales. Entre los 7 y 12 primeros días de evolución después de concluido el ciclo de tratamiento de los diferentes citostáticos el crecimiento volumétrico resultó lento en relación con los controles, y no rebasó en este periódo 0,7 cm3

Psoriasis, razoxane and a cutaneous B-cell lymphoma.

A woman with a 20-year history of acral pustular psoriasis of Hallopeau and recurrent pustular lesions of the forearms and lower legs, developed a B-cell lymphoma of the lip following 4 1/2 years of treatment with razoxane.