Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals

OBJECTIVE: The aim of our study was to evaluate human papillomavirus (HPV) infection as a risk factor for cutaneous squamous cell carcinoma (SCC) in immunocompetent individuals. DESIGN: Hospital-based case-control study. SETTING: Referral center for dermatologic diseases for central and southern Italy. PARTICIPANTS: Consecutive patients with histologically confirmed cutaneous SCC (n = 46) and control subjects (n = 84) chosen by frequency matching (age and sex) among patients admitted with unrelated diseases. MAIN OUTCOME MEASURE: Infection with epidermodysplasia verruciformis-related HPV types, blindly assessed by serologic testing (viruslike particle enzyme-linked immunosorbent assay). Information was obtained on known potentially confounding risk factors (family history, history and signs of sun exposure, and pigmentary traits) and on history of HPV-related lesions and diseases, assessed by interview and examination by a dermatologist. RESULTS: Positive serologic findings for HPV type 8 were associated with SCC (odds ratio, 3.2; 95% confidence interval, 1.3-7.9) independently of other risk factors, whereas positive serologic findings for HPV type 15 were negatively associated with SCC (odds ratio, 0.4; 95% confidence interval, 0.2-0.9). Other variables significantly associated with the tumor were family history of skin cancer, professional or recreational sun exposure, light eye color, high number of solar keratoses and seborrheic keratoses on the body surface, and residency in radon-emitting buildings. CONCLUSIONS: Positive serologic findings for HPV type 8 are associated with SCC occurrence in immunocompetent individuals. Viral infection could act as a cofactor in the tumor development, along with genetic predisposition, solar radiation, and other environmental exposures. If confirmed, these findings could open new perspectives for treatment and prevention of SCC.     

Vulvar manifestations of human papillomavirus infection.

As technology continues to improve, we are increasingly able to detect the presence of HPV in both clinically diseased and histologically and clinically normal vulvar tissue. Unfortunately, the technology for effective treatment of these conditions has not advanced as rapidly. Still, fundamental information about the interaction of HPV with the host cell continues to be collected and will provide us with an increased understanding of the importance of latent infection and its progression to clinical vulvar disease. There are a host of therapeutic modalities available for the treatment of HPV-associated conditions of the vulva, ranging from simple topical medication like podophyllin to sophisticated combination therapies involving carbon dioxide laser destruction in conjunction with interferon. Regrettably, there is no "magic bullet" that is totally effective for any of the HPV-associated vulvar diseases. This makes it more important to weigh the benefits and morbidity of treatment regimens before they are used. Until the success rate of available therapies improves, it is important to have definitive goals for therapy, because it is currently impossible to completely eradicate HPV from tissues. Examples of therapeutic goals might range from removal of visible lesions or treatment of symptomatic areas to treatment of premalignant or malignant lesions. At present, perhaps the most important service we can provide for patients is close follow-up of HPV-associated vulvar diseases in an attempt to prevent the development of invasive malignancy. Regardless of the choice of treatment, the primary objective of the clinician should be to help the patient but to do no harm.     

Oral verrucous carcinoma and human papillomavirus infection

BACKGROUND: Verrucous carcinoma of the oral cavity is a clinical variant of squamous cell carcinoma. Infection with human papillomavirus (HPV) seems to be a significant risk factor in carcinogenesis, as illustrated in our case report. PATIENTS AND METHODS: A 72 year-old woman with a history of actinic cheilitis consulted for a bulky tumour of the lips and palate. Clinical examination revealed a highly infiltrated labial tumour vegetating and budding, with a thick edge. A bulky tumour and firm masses were seen on the hard and soft palates. Biopsy samples from both sites indicated well-differentiated veruccous epidermoid carcinoma with chorionic infiltration. The immunohistochemical study showed intestinal tumour containing HPV-16 virus. The central facial scan showed involvement of the nasal fossae, soft palate and lips with lysis of the upper maxilla arcade and the osseous palate. The patient died a few days before the start of preoperative chemotherapy following severe deterioration of her general state. DISCUSSION: Verrucous carcinoma is an authentic well-differentiated low-grade cancer. It appears as a wart-like exophytic lesion and progresses over several years. Diagnosis is based on histological examination. Management and treatment are not codified but surgery remains the treatment of choice and relapse is common in the case of locoregional involvement.     

Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome

BACKGROUND: Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). OBJECTIVE: To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. METHODS: Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. RESULTS: Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV- induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. CONCLUSIONS: The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients.     

人乳头瘤病毒感染的预防和治疗进展

人乳头瘤病毒是一种环状双链DNA病毒.部分亚型可特异性地感染肛门生殖器皮肤和黏膜,导致生殖器疣和鳞状上皮内皮损等良恶性病变.宫颈持续的高危型人乳头瘤病毒感染是宫颈癌发生的必要条件.目前可用于治疗人乳头瘤病毒感染的方法主要有预防性疫苗、杀微生物剂、局部免疫调节剂、治疗性疫苗等.概述近年来针对人乳头瘤病毒的治疗进展.     

皮肤鳞状细胞癌中人乳头瘤病毒的检测

目的:检测皮肤鳞状细胞癌(SCC)皮损中的人乳头瘤病毒(HPV)并探讨其在SCC发病中的作用.方法:用原位杂交(ISH)、聚合酶链反应技术(PCR)检测SCC患者43例,健康者28例标本组织切片中的HPV6、11、16、18、31、33.结果:43例SCC中有2例肢端部位皮损呈HPV DNA阳性,检出类型为HPV16和HPV33.其中1例标本中HPV16和HPV33同时阳性.对照组全部为阴性.结论:HPV16等6种黏膜型HPV可能与肢端以外SCC的发生无相关性,而与肢端部位SCC可能有关联性.     

Detection of human papillomavirus in cutaneous extragenital Bowen's disease in immunocompetent patients

INTRODUCTION: A specific link between human papillomavirus (HPV) types 16, 18, 31, and 33 and genital carcinomas and between HPV type 5 and cutaneous extragenital carcinomas in patients with epidermodysplasia verruciformis and renal transplant has been previously found. The aim of this prospective study was to detect HPV in cases of cutaneous extragenital Bowen's disease (BD) from non-immunosuppressed patients. PATIENTS AND METHODS: Twelve cases of cutaneous extragenital BD or Bowen's carcinoma (BC), seen in the period 1994-1996 and confirmed by histologic examination, were included in the study. Tissue sections were studied by in situ hybridization with a mixture of HPV DNA probes and specific HPV DNA probes. In addition, study on fresh materiel from 1995 included: Southern blot hybridization with various usual HPV probes (6, 11, 16, 18, 31, 33, 35, 39, 42), polymerase chain reaction (PCR) with hybridization using consensus HPV probes and probes specific for HPV types 6, 11, 16, 18 and 33. In positive samples with conventional PCR, in situ PCR with probes specific for HPV types 6/11 and 16 was performed on tissue sections. RESULTS: In situ hybridization was negative in all the cases. Southern blot hybridization was negative in our 9 studied cases. Three cases studied by consensus PCR were positive. PCR with specific HPV probes revealed positivity on two of these cases: HPV 6 in one, and HPV 16 in another. In situ PCR was positive with a mixed 6/11 HPV probe in the third positive consensus PCR case. DISCUSSION: Our study revealed the presence of HPV in 3 out of 12 cases of cutaneous extragenital BD and BC. HPV type 16, found in BC of skull, was the most usually found type in the literature. HPV types 6/11, detected in 2 cases, were rarely found in cutaneous extragenital BD and BC and these results are in favor of the oncogenic effect of these virus types. In our study, in situ hybridization and Southern blot hybridization were negative in all the cases; HPV was only found in 3 cases by conventional PCR and in 1 case by in situ PCR. The low range of detection of HPV in cutaneous extragenital BD may be due to the used methods, to difficulties related to sampling and/or to a low number of copies of the HPV genoma.     

132例皮肤疣组织人乳头瘤病毒分型检测

目的 探讨皮肤疣组织中人乳头瘤病毒（HPV）的感染率和病毒型别。方法 门诊皮肤疣患者132例中寻常疣46例,跖疣38例,扁平疣48例。以特异性DNA序列为模板设计引物,进行PCR扩增,电泳,对结果进行分析。 结果 132例皮肤疣中,HPV阳性128例,感染率为97.0%,其中HPV2型阳性111例,感染率为84.1%。寻常疣、跖疣感染主要为HPV2、HPV1型,扁平疣感染主要为HPV2、HPV10、HPV3、HPV1型。89例为多重感染,感染率为67.4%,其中二重感染率为41.7%（55例）,三重感染率为21.2%（28例）,四重感染率为4.6%（6例）;寻常疣多重感染率为50.0%（23/46）,跖疣为76.3%（29/38）,扁平疣77.1%（37/48）。多重感染中,以HPV1 + 2型最多,有35例（39.3%）,其次为HPV1 + 2 + 10型,有12例（13.5%）。 结论 遵义皮肤疣感染以HPV2型为主,其次为1型;2型与多种皮肤疣感染有关;皮肤疣中多重感染率较高,其中扁平疣多重感染率最高;新发现HPV3、10型感染寻常疣,HPV10型感染跖疣,HPV1、7型感染扁平疣。     

Epidermodysplasia verruciformis-associated papillomavirus infection complicating human immunodeficiency virus disease

Three males infected with the human immunodeficiency virus (HIV) were noted to have extensive flat warts of the face and/or body. In two there were also pityriasis versicolor-like lesions. Biopsies showed foamy, basophilic, distended cytoplasm in granular layer keratinocytes, characteristic of the human papillomavirus types seen in epidermodysplasia verruciformis. DNA hybridization techniques demonstrated the presence of HPV-type 8 in one patient and HPV 5 and 8 in another. Patients with immune suppression due to HIV infection may demonstrate the clinical features of epidermodysplasia verruciformis with the same potentially oncogenic HPV types.     

Ubiquitination in host immune response to human papillomavirus infection

Human papillomavirus (HPV) infection with low-risk or high-risk subtypes is very common. Infection with HPVs is often a major causative factor for the development of cutaneous benign lesions, cervical cancer, and a number of other tumors. The mechanisms of host immunity to prevent and control HPV infection still remain unclear. The importance of ubiquitination (or ubiquitylation) as an intracellular proteasomal-mediated protein degradation pathway, and as an important modulator for the regulation of many fundamental cellular processes has been valued over the last decade. Although the molecular and cellular mechanisms are not completely established, the critical role of ubiquitination in host immune response to HPV infection has become increasingly apparent. This review summarizes current knowledge on the possible role that ubiquitination plays in regulating the host immune response during HPV infection. Targeting the components of the ubiquitin system might offer potential therapeutic strategies for HPV-related diseases in the future.