[Show abstract][Hide abstract] ABSTRACT: Previously, we have shown that immunization with human papillomavirus (HPV) type 16-derived cytotoxic T lymphocyte (CTL) epitope E7 49-57 (RAHYNIVTF) renders C57BL/6 mice insensitive to tumors formed by HPV16-transformed cells. In this study, we provide evidence that E7 49-57 is expressed as a subdominant CTL epitope on HPV16-transformed C57BL/6 cells. Using acid peptide elution, it is shown that HPV16-transformed cells express another CTL epitope, besides E7 49-57, which appears to be dominant. We demonstrate that a CTL line raised against the subdominant CTL epitope, offered as synthetic peptide E7 49-57, eradicates established HPV16-induced tumors in mice. Our data show that synthetic peptide-induced CTL can be applied successfully in vivo against (virus-induced) tumor, and emphasize that subdominant CTL epitopes are useful targets for immunotherapy. Furthermore, it is illustrated for the first time that HPV16-specific CTL interfere directly with HPV16-induced tumors.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological data on cutaneous wart-associated HPV types are rare.
To examine the prevalence of cutaneous wart-associated HPV types and their relation with patient characteristics.
Swabs were taken from all 744 warts of 246 consecutive immunocompetent participants and analysed by a broad spectrum HSL-PCR/MPG assay. Patient details including location, duration, and number of warts were recorded.
No HPV DNA was detected in 49 (7%) swabs, a single HPV type in 577 (78%) swabs, and multiple HPV types in 118 (16%) swabs. HPV 2, 27 and 57 (alpha genus), HPV 4 (gamma genus) and HPV 1 (mu genus) were the most frequently detected HPV types, and HPV 63 (mu genus) was only frequently detected together with other HPV types. Less frequently detected HPV types were HPV 3, 7, 10 and 28 (alpha genus), 65, 88 and 95 (gamma genus) and 41 (nu genus). Warts containing HPV 1 showed the most distinct clinical profile, being related to children aged <12 years, plantar location, duration <6 months, and to patients with <4 warts.
HPV 27, 57, 2 and 1 are the most prevalent HPV types in cutaneous warts in general population. Warts infected with HPV 1 have a distinct clinical profile.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2012; 55(3):250-5. DOI:10.1016/j.jcv.2012.07.014 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Large numbers of HPV types infect the human skin and members from the HPV genera alpha, gamma and mu are associated with cutaneous warts.
The aim of this study was to test if the HPV genotypes in swabs of the overlying skin are identical to the types present within these warts.
To this purpose, 25 persons being treated for persistent cutaneous warts were enrolled. Swabs of the overlying skin of the wart were collected from each participant. Additionally, scabs of the wart and deeper portions of the warts were surgically removed. HPV genotyping was performed on all samples using the novel HSL-PCR/MPG assay and the HPV genotyping results were compared.
From the 25 wart biopsies one was HPV negative. 15 were positive for HPV27, 3 for HPV57, 2 for HPV2, 2 for HPV1, 1 for HPV3 and 1wart biopsy was positive for both HPV41 and HPV65. Scabs and swabs of the warts both showed identical typing results as the biopsies in 24 of the 25 cases (sensitivity: 96%).
There was an excellent agreement between HPV types in the swabs of the skin that overlies the warts and the biopsies of these warts validating the use of wart swabs for future studies of wart-associated HPV types. HPV27 was highly prevalent (70%) in the in adults of the investigated population of patients with persistent cutaneous warts.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2011; 52(2):84-7. DOI:10.1016/j.jcv.2011.06.016 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.
American Journal of Transplantation 07/2011; 11(7):1498-508. DOI:10.1111/j.1600-6143.2011.03589.x · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case-control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case-control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma.
Cancer Research 12/2010; 70(23):9777-86. DOI:10.1158/0008-5472.CAN-10-0352 · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies revealed that Betapapillomavirus (betaPV) infections are highly prevalent. Skin diseases such as psoriasis, characterized by keratinocyte hyperproliferation, and atopic dermatitis (AD), dominated by cutaneous inflammation, might have an impact on viral life cycle and immune response induction.
To investigate whether betaPV infection is different in psoriasis and AD.
Twenty-seven patients with psoriasis and 17 with AD were included for betaPV genotyping using eyebrow hairs, and for seroresponse determination.
BetaPV DNA was found significantly more often in patients with psoriasis than in those with AD (100% vs. 81%, P=0·022) and the mean number of betaPV types was higher (4·8 vs. 2·1 types, P=0·002). In contrast, the seroprevalence in patients with AD was significantly higher compared with that in patients with psoriasis (88% vs. 56%, P=0·023). Type-specific concordance of serological response to the betaPV type detected in eyebrow hairs was 27% in patients with psoriasis and 47% in those with AD (P=0·019).
We speculate that the condition of the skin and the immunological state of the patients have an important impact on the life cycle of betaPV.
British Journal of Dermatology 12/2010; 164(4):771-5. DOI:10.1111/j.1365-2133.2010.10182.x · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A large number of human papillomavirus (HPV) types, distributed over five papillomavirus genera, are detectable in the skin. HPV types belonging to the alpha, gamma, and mu genera have been detected in cutaneous warts. A state-of-the-art HPV genotyping assay for these cutaneous wart-associated HPV types does not exist although warts constitute a highly prevalent skin condition, especially in children (33%) and organ transplant recipients (45%). Cutaneous warts are again the focus of attention as their clinical relevance rises with the increasing number of chronically immunosuppressed patients. The objective of this study was to develop and evaluate a DNA-based genotyping system for all known cutaneous wart-related HPV types using PCR and Luminex xMAP technology. The broad-spectrum PCR amplified DNA of all known wart-associated HPV types from the genera alpha (HPVs 2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91, and 94), gamma (HPVs 4, 65, 95, 48, 50, 60, and 88), mu (HPVs 1 and 63), and nu (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterized cutaneous wart biopsy specimens showing high specificity. HPV was also identified in 96% of 100 swabs from nongenital cutaneous warts. HPV types 1, 2, 27, and 57 were the most prevalent HPV types detected in 89% of the swabs. In conclusion, this Luminex-based genotyping system identifies all known cutaneous wart HPV types including phylogenetically related types, is highly HPV type specific, and is suitable for large-scale epidemiological studies.
[Show abstract][Hide abstract] ABSTRACT: Human papillomaviruses from the genus beta (betaPV) are a possible cause of cutaneous squamous cell carcinoma (SCC). We compared the betaPV infections in SCC and in sets of cutaneous tissues collected from a series of individual SCC patients to determine concordance and to assess the adequacy of eyebrow hairs as noninvasive markers of betaPV infection. Biopsies of SCC tumors, perilesional tissue, normal skin from the mirror image of nonfacial SCC and plucked eyebrow hairs were collected from 21 patients with incident SCC living in Queensland, Australia. These were tested for the presence of DNA from 25 different betaPV types. Overall prevalence of betaPV was high in every sample type, ranging from 81% to 95%. The median number of types was significantly higher in the SCC tumour (6), perilesional skin (5) and eyebrow hairs (5) than in normal skin (2). Comparing SCC tissue with other sample types within patients showed 63 overlapping infections with eyebrow hairs (71%; 95% CI: 60-80); 56 with perilesional skin samples (63%; 95% CI: 52-73) and 23 with normal skin samples (26%; 95% CI: 17-36). The sensitivity of eyebrow hair testing for detection of betaPV in the tumor was 82% (95% CI: 57-96) with concordance defined as 50% of betaPV types in common and 29% (95% CI: 10-56) for 100% concordance. These findings support the concept that perilesional skin represents an area of field change involving betaPV preceding SCC development and indicate that eyebrow hairs can serve to some degree as an easily collected marker of tumor betaPV status in epidemiological studies.
International Journal of Cancer 01/2010; 126(11):2614-21. DOI:10.1002/ijc.24991 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Betapapillomavirus (betaPV) infections are often associated with squamous-cell carcinoma (SCC) and the prevalence of betaPV infections in (immunosuppressed) SCC patients is known to be high. The distribution and possible associated factors of betaPV infections in the general population, however, are largely unknown. To address this issue, betaPV infection was studied in 1405 SCC-free immunocompetent (n=845) and immunosuppressed (n=560) individuals from six countries of different latitudes. A standard study protocol was used to obtain information about age, sex, UV-irradiation and skin type, and from all participants eyebrow hairs were collected for detection and genotyping of 25 established betaPV types using the PM-PCR reverse hybridization assay (RHA) method. The frequency of betaPV-positive participants ranged from 84 to 91% in the immunocompetent population with HPV23 as the most prevalent type, and from 81 to 98% in the immunosuppressed population with HPV23 as the most or the second most prevalent type. The median number of infecting betaPV types ranged from four to six in the immunocompetent and from three to six in the immunosuppressed population. Increasing age in the immunocompetent participants and (duration of) immunosuppression in the immunosuppressed patients were associated with betaPV infection. In both groups, sex, skin phototype, sunburns and sun-exposure were not consistently associated with betaPV infection. This study demonstrates that betaPV infections are also highly prevalent in SCC-free individuals, with similar HPV types prevailing in both immunocompetent and immunosuppressed persons. Age and (duration of) immunosuppression were identified as betaPV infection-associated factors, whereas characteristics related to sun exposure and skin type were not.
Journal of General Virology 04/2009; 90(Pt 7):1611-21. DOI:10.1099/vir.0.010017-0 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).
We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction-reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples (P = 0.046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2-8). Tumours from IS patients were from a younger age group (mean age 57.4 years) than IC patients (mean age 73.8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) (P < 0.001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.
British Journal of Dermatology 03/2009; 161(1):56-62. DOI:10.1111/j.1365-2133.2009.09146.x · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomaviruses (HPV) are found in almost all squamous epithelia where they can cause hyperproliferative disease of mucosa and skin. Mucosal HPV types, such as HPV6 and HPV16, are known to cause anogenital warts and dysplasia or neoplasia, respectively. These HPV types have been studied extensively, and for some of them recently preventive vaccines have become available. Although HPV that populate the skin were the first identified HPV types, knowledge of the pathogenicity of HPV in the cornified epithelia stayed behind. What the majority of cutaneous HPV types do, for instance those belonging to the beta genus (betaPV), is largely unknown. As the number of reports that describe epidemiological associations between markers of betaPV infection and skin cancer gradually increases, the need for basic knowledge about these viruses grows as well. This review aims to picture what is currently known about betaPV with respect to infection, transmission and transformation, in order to envisage their potential role in cutaneous carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 in vitro, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8- and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.
Journal of General Virology 10/2008; 89(Pt 9):2303-14. DOI:10.1099/vir.0.83317-0 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infections with human papillomaviruses (HPVs) belonging to the genus Betapapillomavirus have been linked to the development of non-melanoma skin cancer. Although persistence is expected, systematic investigation of this aspect of betapapillomavirus (beta-PV) infection has not been conducted. This study investigated the prevalence and persistence of 25 known beta-PV types in the skin of immunocompetent individuals. Over a 2 year period, eight consecutive plucked eyebrow hair samples taken from 23 healthy individuals were analysed for the presence of beta-PV DNA. Using a recently published general beta-PV PCR and genotyping method, 61% of the individuals were beta-PV DNA positive for one or more types at intake, whereas during follow-up this percentage rose to 96%. HPV23 was the most frequently detected beta-PV type. Type-specific beta-PV DNA was detected over 6 months or longer in 74% of the individuals. In 57% of the individuals, DNA from multiple beta-PV types was detected simultaneously for 6 months or longer. When the detection intervals of all beta-PV type-specific infections in the study population were considered, a substantial proportion, 48%, lasted at least half a year. The consistent beta-PV patterns found over time in most individuals strongly suggested that beta-PV DNA detection in plucked eyebrow hairs reveals true beta-PV infection. If the minimum interval of detection was set at 6 months, persistent beta-PV infections were found in the majority of the study population (74%).
Journal of General Virology 06/2007; 88(Pt 5):1489-95. DOI:10.1099/vir.0.82732-0 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus can be detected by amplification of viral DNA. A novel one-step PCR (PM-PCR) was evaluated for amplification of a 117-bp fragment from the E1 region. It permitted ultrasensitive detection of all 25 known human papillomavirus genotypes from the beta-papillomavirus genus. The intra- and intertypic sequence variations of the 77-bp interprimer region were studied. Genotype-specific probes as well as general probes were selected for the 25 established beta-papillomavirus types, and a reverse hybridization assay (RHA) was developed (PM-PCR RHA method). The analytical sensitivity of the PM-PCR RHA method was 10 to 100 viral genomes. The one-step PM-PCR turned out to be more sensitive than the previously described nested MaHa-PCR for beta-papillomavirus detection. The PM-PCR RHA method was able to detect and identify beta-papillomavirus types in frozen patient material as well as in poorly amplifiable material such as formalin-fixed, paraffin-embedded skin biopsy specimens. Inter- and intralaboratory variability experiments showed that the reproducibility of the assay was very high. In conclusion, the one-step PM-PCR together with the RHA allows extremely sensitive, specific, and reproducible detection of beta-papillomavirus DNA as well as reliable identification of beta-papillomavirus genotypes in both fresh and paraffin-embedded patient material.
[Show abstract][Hide abstract] ABSTRACT: Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.
[Show abstract][Hide abstract] ABSTRACT: At present, human papillomavirus (HPV) infection is chiefly known for its causal relationship with cervical cancer. Apart from genital types, the papillomavirus family consists of numerous human cutaneous types. The majority belongs to the so-called epidermodysplasia-verruciformis(EV)-HPV types that are potentially involved in skin cancer development. Non-melanoma skin cancers, especially cutaneous squamous cell carcinoma contain HPV DNA (30-60%). In immune-suppressed organ transplant recipients this percentage increases up to 90. Recent epidemiological studies show a statistically significant association between EV-HPV infection and squamous cell carcinoma. In addition recent experimental studies show specific EV-HPV types have a potential to transform cells that is comparable to high-risk genital HPV types. These data indicate that cutaneous HPV infections and squamous cell carcinoma development are associated.
Nederlands tijdschrift voor geneeskunde 04/2005; 149(10):518-22.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies, which address the role of human papillomavirus (HPV) in the pathogenesis of (pre)malignant cutaneous lesions, focus on the HPV B1 subgroup comprising the so-called epidermodysplasia verruciformis (EV)-associated HPV types. To detect and type HPV DNA in human materials, Polymerase Chain Reaction (PCR)-based assays are used. In this chapter, a nested, broad-spectrum PCR method using a mixture of primers and a type-specific PCR using specific primers are described. The broad-spectrum PCR detects the B1 subgroup of HPV types. HPV typing is performed by sequence analysis of the PCR product. The type-specific PCR detects and types HPV 5a, 8, 15, 17, 20, 24, 36, and 38. These HPV types are representative of the B1 subgroup, because they are evenly distributed over the phylogenetic tree of the B1 subgroup.
Methods in molecular medicine 02/2005; 119:115-27. DOI:10.1385/1-59259-982-6:115
[Show abstract][Hide abstract] ABSTRACT: A role for cutaneous human papillomaviruses (HPV) has been proposed in the development of skin cancer. Well-designed epidemiologic studies to demonstrate an association between HPV infection and skin cancer are extremely rare. To identify HPV infection as a potential risk factor, we investigated the association between the presence of HPV DNA in eyebrow hairs and a history of cutaneous squamous cell carcinoma. A case-control study was designed consisting of 155 immunocompetent individuals with a history of squamous cell carcinoma and 371 controls without skin cancer. DNA extracted from plucked eyebrow hairs collected from the study population was analyzed with a cutaneous HPV subgroup polymerase chain reaction and newly designed HPV type specific polymerase chain reactions for HPV 2, 5, 8, 15, 16, 20, 24, and 38. HPV DNA was detected in 63.1% of the total study population. The presence of HPV DNA was associated with age (p=0.0002) and male sex (p=0.02), but not with sun exposure, skin type, and smoking. After adjustment for age and sex, the presence of HPV DNA in eyebrow hairs was associated with a history of squamous cell carcinoma (odds ratio 1.7, 95% confidence interval 1.1; 2.7). HPV type specific analysis revealed that no HPV type stood out. The high-risk mucosal type HPV 16 and the skin wart type HPV 2 were rarely found in this study (<0.2%). The positive association found between the presence of HPV DNA in eyebrow hairs and a history of squamous cell carcinoma warrants further research into the role that HPV infection plays in the development of cutaneous squamous cell carcinoma.
[Show abstract][Hide abstract] ABSTRACT: DNA from epidermodysplasia verruciformis-related human papillomavirus (EV-HPV) types is frequently found in nonmelanoma skin cancer (squamous and basal cell carcinoma). Epidemiological studies that investigate the relation between EV-HPV infection and nonmelanoma skin cancer are scarce. We designed a case-control study in which we looked for HPV infection in 540 cases with a history of skin cancer and 333 controls. By measuring seroreactivity to L1 virus-like particles of EV-HPV types 5, 8, 15, 20, 24, and 38 and the genital type HPV16 and by estimating the skin cancer relative risk among HPV seropositives, we analyzed whether EV-HPV serorecognition is associated with nonmelanoma skin cancer. Seroreactivity to five of the six EV-HPV types tested (HPV5, 8, 15, 20, and 24) was significantly increased in the squamous cell carcinoma cases. After adjusting for age and sex, the estimated squamous cell carcinoma relative risk was significantly increased in HPV8 and HPV38 seropositives [odds ratio (OR) = 14.7 (95% confidence interval (CI), 1.6-135) and OR = 3.0 (95% CI, 1.1-8.4), respectively]. The estimated relative risk for nodular and superficial multifocal basal cell carcinoma was also significantly increased in the HPV8 seropositives [OR = 9.2 (95% CI, 1.1-78.2) and OR = 17.3 (95% CI, 2.1-143), respectively] and in the HPV20 seropositives [OR = 3.2 (95% CI 1.3-7.9) and OR = 3.4 (95% CI 1.2-9.5), respectively]. The relative risk of developing malignant melanoma was not increased among HPV seropositives, and no associations were found for HPV16. Restricted analyses among the HPV seropositives only, to exclude distortion by interindividual differences in seroresponsiveness, underscored the significance of our findings. Restricted analyses among patients with skin cancer only, however, revealed that EV-HPV seropositivity was not significantly more present in patients with nonmelanoma skin cancer than in those with melanoma skin cancer. Taken together, our results indicate that EV-HPV serorecognition is nonspecifically associated with nonmelanoma skin cancer and suggest that EV-HPV-directed seroresponses are induced upon skin cancer formation, rather than upon infection.
Cancer Research 06/2003; 63(10):2695-700. · 9.28 Impact Factor