Serological association of beta and gamma human papillomaviruses with squamous cell carcinoma of the skin

Background  Cutaneous human papillomaviruses (HPVs) may play a role in the development of squamous cell carcinomas (SCC) of the skin.
Objectives  Available serological studies on HPV and skin SCC have analysed only few HPV types from the phylogenetic genus beta. The potential association of cutaneous HPV types from the genera alpha, gamma, mu and nu with skin SCC has not been thoroughly analysed so far.
Methods  Using multiplex serology, a method that allows analysing sera for antibodies to up to 100 different antigens simultaneously, we re-analysed an SCC case–control study in immunocompetent individuals (43 cases, 77 controls) for antibodies to L1 capsid proteins of 29 cutaneous and two mucosal HPV types from five different genera.
Results  Significantly increased SCC risks were observed for the beta HPV types 15, 17 and 38, as well as for the gamma HPV type 50, with type-specific odds ratios (ORs) ranging from 2·6 to 3·4. Significant associations were also found in cases of seropositivity for any type of the beta 2 species (OR 3·3, 95% confidence interval [CI] 1·2–8·7) and for any type of the gamma genus (OR 3·1, 95% CI 1·1–8·6). With regression models that included all HPV types and forward stepwise selection, two gamma HPV types (HPV 95, OR 25, 95% CI 1·2–509; HPV 50, OR 3·6, 95% CI 1·4–9·4) were each significantly associated with skin SCC.
Conclusions  Our study confirms a possible role of cutaneous HPV in the development of skin SCC. Future studies should include skin HPV types from more than only the beta genus, especially gamma types.     

Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Diversity of human papillomavirus types in periungual squamous cell carcinoma

Background There is accumulating evidence that infections with certain high‐risk α‐human papillomaviruses (HPVs) are involved in the pathogenesis of digital squamous cell carcinomas (SCCs) and their precursor lesions (SCCs in situ). Objectives This study was initiated to search for α‐ and β‐HPV infections in a collective of SCC and SCC in situ located on the hands. Methods HPV typing for 36 high‐risk and low‐risk α‐HPV types and 25 β‐HPV types was performed in SCCs located at different sites of the hands. Additionally, immunohistochemical staining for p16^INK4a and Ki67 was performed in 15 samples. Results In total, 25 SCCs/SCCs in situ (six periungual lesions, eight lesions from the proximal or lateral part of the finger, and 11 lesions from the dorsal part of the hand) were analysed for the presence of α‐ and β‐HPV types. Only one lesion (an SCC in situ positive for HPV11 and HPV31) of the dorsal hand and none of the proximal or lateral part finger lesions were α‐HPV positive. In contrast, all six periungual lesions were α‐HPV positive, and the majority (83%) of them carried HPV types other than HPV16 (HPV26, HPV33, HPV51, HPV56 and HPV73). β‐HPV types were found in only two biopsies. p16^INK4a and Ki67 expression was significantly higher in HPV‐positive lesions as compared with HPV‐negative tumours, and both markers significantly correlated with each other. Conclusions In contrast to other locations of the hands, periungual SCCs are frequently associated with α‐HPV infections. Several high‐risk HPV types other than HPV16 can induce periungual SCCs. Given the high recurrence rate and high proliferative activity of HPV‐associated periungual SCCs, aggressive treatment and close follow‐up of these tumours is mandatory.     

Detection of high-risk human papillomaviruses in verrucae of patients with mycosis fungoides and Sézary syndrome: a case series

Background  Mycosis fungoides (MF)/Sézary syndrome (SS) patients are immunocompromised and thus may be susceptible to high-risk human papillomavirus (HPV) infections that are difficult to treat.
Methods  Three patients with verrucous skin lesions, 2 of whom had coexisting squamous cell carcinoma (SCC) near the verruca biopsy site, had biopsies of verruca for histologic examination. HPV typing was performed on fresh verruca biopsies by nested polymerase chain reaction.
Results  A single type of high-risk HPV was identified in each patient's lesion.
Conclusions  HPV may have acted as a cocarcinogen in the development of SCC in two patients and extensive condyloma acuminatum in one.     

Immunohistochemical staining of p16 in squamous cell carcinomas of the genital and extragenital area

Background and objectivesPositive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or αsubtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC.Material and methodsParaffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR).ResultsIn the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages.ConclusionsAccording to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.     

Mucosal human papillomavirus types in squamous cell carcinomas of the uterine cervix and subsequently on fingers

Human papillomavirus (HPV), especially type 16, is causally involved in the pathogenesis of anogenital cancer. There is an increasing number of reports of HPV infections in squamous cell carcinoma (SCC) of the fingers. A search of the Swedish cancer register covering the period 1958-94 inclusive for women with a history of genital and upper extremity SCC revealed 63 cases. Archival material from both cervical and cutaneous lesions was traced and analysed for the presence of HPV DNA in 32 of these patients. A newly developed 'neighbour primer' polymerase chain reaction (PCR) for HPV 16 DNA, aimed at overcoming the obstacle of cross-linked target DNA, was shown to be superior to conventional general and type-specific HPV PCR tests. HPV DNA was significantly more frequently found in digital tumours than in tumours at other cutaneous sites of the upper extremities [67% (10 of 15) vs. 7% (three of 43); P < 0.001]. Among 13 patients with a history of both cervical and finger SCC, HPV 16 was found in cervical samples from seven patients. From five of these seven patients, HPV 16 was also present in the corresponding finger lesions. The results support the hypothesis of a possible transmission of patients' genital HPV infections to fingers.     

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.     

Penile cancer among patients with genital lichen sclerosus

BACKGROUND: Genital lichen sclerosus (LS) has sporadically been reported to be associated with penile squamous cell carcinoma (SCC). OBJECTIVE: The purpose of this study was to assess the risk of malignant degeneration in a series of male patients affected by genital LS. METHODS: All cases of histologically proven epithelial malignancy associated with penile LS recorded in our pathology files over a 10-year period (1987-1997) were reviewed. Assessment for presence of human papillomavirus (HPV) was performed from paraffin-embedded tissues using polymerase chain reaction (PCR). RESULTS: Five of 86 white and uncircumcised men with genital LS (mean age at diagnosis, 53 years; range, 22-83 years) showed malignant or premalignant histopathologic features: 3 had SCC, one had erythroplasia of Queyrat (unifocal SCC in situ), and one verrucous carcinoma. The average lag time from onset of LS was 17 years (range, 10-23 years). Histologically, transition from LS to frank neoplastic foci was evident in all cases of SCC. In these SCC cases, areas of epithelial dysplasia were well evident at the tumor periphery. In the remaining cases, the histologic findings were consistent with erythroplasia of Queyrat and verrucous carcinoma. PCR detected HPV 16 infection in 4 of the 5 cases; one SCC patient was negative for HPV. CONCLUSION: Malignant changes were associated with 5.8% of the cases of penile LS in our series. Therefore patients with genital LS are at considerable risk of the development of penile SCC, as well as other epithelial and in situ carcinomas, namely verrucous carcinoma and erythroplasia of Queyrat. HPV infection probably plays a major role because 4 of 5 patients were positive for HPV. Histologically, epithelial dysplasia may represent a precancerous stage before the development of neoplasia in atrophic nonproliferative LS lesions, as its presence at the tumor periphery in our SCC biopsy samples seemed to suggest.     

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.     

Prevalence status and association with human papilloma virus of anal squamous proliferative lesions in a patient sample in Taiwan

BACKGROUND AND OBJECTIVE: Anal squamous proliferative lesions, including condyloma, anal high-grade squamous intraepithelial lesion (AHSIL) and squamous cell carcinoma (SCC), are associated with human papilloma virus (HPV) infection. The objectives of the study were to investigate the HPV prevalence of anal squamous proliferative lesion in Taiwan. STUDY DESIGN: From 1991 to 2005, 41 cases with condyloma, 12 cases with AHSIL, and 13 cases with SCC were collected. DNA was extracted from the tissue sections of these patients, and the HPV genotype was identified using polymerase chain reaction and gene chip. The integration status of HPV16 DNA was also evaluated by quantitative real-time polymerase chain reaction. RESULTS: Anal condyloma mainly occurred in young males, but AHSIL and anal SCC developed in older patients. In the patients with human immunodeficiency virus (HIV) infection, AHSIL developed much earlier than patients without HIV infection (36 vs. 61 years). HPV DNA was detected in all 56 patients whose specimens contained adequate DNA. High-risk HPVs (type 16, 58, etc.) were mainly detected in the AHSIL and SCC. Multiple HPV infection was found in AHSIL (4 of 12) and condyloma (11 of 34) but was rare in invasive cancer (1 of 12). Seven of 8 patients with HPV16 infection had coexistent episomal and integrated forms. CONCLUSION: HPV58 is a unique high-risk HPV prevalent in Taiwan. The integration status of HPV seems not correlated with the severity of the dysplasia. In our study, emerging HIV-positive AHSIL in recent years indicates that we should devote more efforts to promote sexual safety among the people who engaged in anal intercourse.     

Evaluation of the role of genital human papillomavirus in the pathogenesis of ungual squamous cell carcinoma.

Human papillomaviruses (HPV), and particularly HPV 16, have been associated with ungual squamous cell carcinoma (USCC). But their role in tumor development remains unclear. In genital carcinoma, where the oncogenic role of HPV is well established, integration of HPV DNA into the host cell genome seems to be important for malignant transformation. To clarify the issue, we have studied the physical state of HPV 16 in 3 cases of in situ USCC by the polymerase chain reaction and by in situ hybridization. HPV DNA was integrated into the human genome in 2 cases and episomal in 1 case. This particular physical state of HPV 16 in USCC, similar to those encountered in anogenital SCC, confirms the probable role of this kind of virus in the pathogenesis of USCC.     

Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases

OBJECTIVE: Our aim was to review the clinical behavior of human papillomavirus (HPV)-associated digital squamous cell carcinoma (SCC). Specifically, we examined evidence for the tumor's (1) infectious origin and spread, (2) response to therapy, and (3) prognosis and metastatic risk. DESIGN: We reviewed and performed data tabulation of all 51 reported cases in the English-language literature and a case series of 23 cases (21 of them not previously reported). We present 2 of the cases in depth. SETTING: We used previously reported cases from MEDLINE and a case series from a single dermatologic operation practice from 1985 to 1999. RESULTS: (1) Of all cases, 10% (7/72) had an antecedent genital dysplasia or carcinoma containing the same HPV subtype as the digital SCC. (2) The rate of recurrence after general surgical therapy was 43% (6/14). After Mohs micrographic surgery the recurrence rate was 13% (2/16) for the cases in the literature, and 26% (6/23) for our case series. (3) Of tumors, 3% (2/72) have been observed to metastasize. CONCLUSIONS: (1) This suggests the possibility of genital-digital spread as a mechanism of tumor genesis. (2) HPV-associated digital SCC is more likely to recur after surgical treatment than previously reported. This rate of recurrence greatly exceeds that for cutaneous SCCs in general and may be caused by residual postsurgical HPV. (3) The rate of metastasis, however, appears to be low.     

Use of the polymerase chain reaction to detect human papillomavirus type 16 in the cervical scrapes of Irish women with varying grades of cervical intraepithelial neoplasia

Objective To assess the prevalence of HPV type 16 among Irish women with various degrees of CIN.
Subjects One hundred and five women with varying degrees of CIN, detected on prior cytological screening, and thirty-two women with cytologically normal cervical smears.
Methods HPV 16 DNA was detected by the PCR technique, with controls against contamination.
Setting The colposcopy clinic in the Rotunda Maternity Hospital, Dublin, and the Virus Reference Laboratory, U.C.D., from October 1991 to April 1992.
Results HPV 16 DNA was detected in 66% of subjects with abnormal cervical cytology, and in 31% of those with normal cervical smears. A higher HPV 16 prevalence was found among those women with CIN III (74%), than among those with CIN I/CIN II (60%).
Conclusions The prevalence of HPV 16 among Irish women with normal cytology and CIN was similar to previous published studies from other areas, with a higher prevalence in those with abnormal cervical cytology. The usefulness of detection of HPV 16 as an indicator of a higher risk of carcinoma of the cervix is discussed.     

The role of p53 codon 72 and human papilloma virus status of cutaneous squamous cell carcinoma in the Swedish population

The arginine variant of the p53 codon 72 polymorphism as well as anogenital and epidermodysplasia verruciformis (EV) types of human papilloma virus (HPV) are suggested to confer increased risk for developing cutaneous squamous cell carcinoma (SCC). In this pilot study, we analysed the p53 codon 72 genotype distribution in 106 microdissected samples from normal and tumour tissues of 53 cases of cutaneous SCC and 96 controls from Sweden. Both normal and tumour samples from cases of SCC were screened for anogenital and EV HPV. The p53Arg allele was not associated with the development of cutaneous SCC. Anogenital HPV (44%) was more prevalent than EV HPV (12%). Data also indicate that anogenital HPV is more common in tumour samples, but HPV infection was not identified as a significant risk factor for developing SCC. The presence of anogenital HPV, but not EV HPV might be a risk factor for development of cutaneous SCC.     

The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

Background  Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.
Methods  Female subjects ( N = 9265) aged 16–24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.
Results  Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8–100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4–100.0).
Conclusion  These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.
NCT0009252, NCT00092534, NCT00092495     

Presence of human papilloma virus type 16 DNA sequences in human nonmelanoma skin cancers

The presence of human papillomaviruses (HPV) has been shown to be associated with the development and progression of invasive cancers of the genital tract, skin, and head and neck. In this study we analyzed 37 human nonmelanoma skin cancers (21 squamous cell carcinomas and 16 basal cell carcinomas) for the presence of HPV sequences. The polymerase chain reaction (PCR) was employed using primers designed to amplify DNA encoding the E6-E7 region of HPV types 6b/11, 16, and 18. HPV type 6b/11 and 18 sequences were absent from the DNA of all 37 tumors examined. However, HPV type 16 sequences were detected in four of 21 squamous cell carcinomas (SCC) (19%) and three of 16 basal cell carcinomas (BCC) (19%) as indicated on agarose gel electrophoresis by the presence of a single specific DNA band of predicted length. Furthermore, HPV type 16 sequences were absent in the DNA of normal skin from these seven skin cancer patients. The presence of HPV type 16 sequences in the seven skin tumors was confirmed by dot blot hybridization of PCR-amplified material to 32P-labeled HPV type 16, but not to HPV type 6/11 or 18-specific probes. These data indicate that HPV type 16, but not 6b/11 or 18, is associated with development of some human nonmelanoma skin cancers.     

Human papillomavirus in cutaneous squamous cell carcinoma and cervix of a patient with psoriasis and extensive ultraviolet radiation exposure

"High-risk" human papillomaviruses (HPVs) are associated with intraepithelial neoplasia and cancer of the uterine cervix. HPV has also been found in nonmelanoma skin cancer (NMSC), especially in squamous cell carcinomas (SCCs) of immunosuppressed patients. Recently, lesions of psoriasis have been shown to harbor HPV, and patients with psoriasis often have a history of extensive therapy with ultraviolet radiation (UVR). UVR is the major known risk factor in the occurrence of NMSC, in which HPV may be a cofactor for SCC. We report an otherwise healthy, nonimmunosuppressed patient with psoriasis who had a history of extensive exposure to UVR and experienced multiple SCCs on UV-exposed body sites. By the polymerase chain reaction method, we detected HPV in 5 of 9 SCCs. Automated sequencing showed HPV types 12 and 17. Only 1 of 3 normal skin specimens was HPV positive (HPV type 17). This positive specimen was from UV-exposed skin; one of the two HPV-negative, normal skin specimens was located on a body site not exposed to sun. In addition, HPV type 62 was found in a brush specimen of the uterine cervix. This case report suggests an association between psoriasis, HPV infection, and UVR exposure, in onset of SCC.     

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.     

Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer

Background Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). Methods One hundred and fifty‐three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case–control study were re‐contacted, and a follow‐up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow‐up period were ascertained. Recurrences and new second cancers were considered together as ‘outcomes’ in time‐to‐event analyses and in Cox proportional hazard models. Results Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV‐24‐seropositive patients with an SCC at baseline had a 4‐fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2–15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found. Conclusions We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case–control studies and may spur further prospective studies on the causal role of HPVs in NMSC.     

Multiple human papillomavirus-16 associated digital squamous-cell carcinomas in an immunocompetent woman with prior human papillomavirus-related genital carcinoma

High-risk subtype human papillomavirus (HPV) infection, which is known to contribute to the oncogenesis of anogenital squamous-cell carcinoma (SCC), is detected in the majority of digital SCCs. Evidence suggests a genital-digital route of transmission of high-risk HPV, and most HPV-related digital SCCs occur near the nail unit in immunocompetent adults. As early HPV-related SCC commonly appears as a verrucous periungual papule, a biopsy should be considered if such a lesion persists or occurs in an individual who is likely to inoculate their digits with high-risk HPV from digital-genital contact with themselves or sexual partners. We present a 60-year-old woman, who has a personal history of vulvar and cervical SCC and an appreciable disease burden from SCCs that involved five digits of her hands.