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.     

Cutaneous squamous cell carcinoma and human papillomavirus

The relationship between mucosal human papillomavirus (HPV) and cervical carcinoma or anogenital squamous cell carcinoma (SCC) is becoming increasingly evident, whereas a link between HPV and other cutaneous SCCs is less clear. Recent studies have reported links between epidermodysplasia-verruciformis-associated HPV and extragenital cutaneous SCC, particularly in immunosuppressed patients, although immunocompetent patients have also been affected. Mucosal HPV could also be linked to some types of Bowen disease and certain SCCs of the fingers, oropharyngeal mucosa, etc. We review the possible oncogenic mechanisms involving mucosal HPV and epidermodysplasia-verruciformis-associated HPV. Most SCCs could be explained by the combined action of HPV, immunosuppression, and the oncogenic and immunosuppressive effect of UV radiation. HPV might be associated with worse prognosis of SCC, with implications for clinical practice including greater risk of metastasis.     

Human papillomavirus type 26 infection causing multiple invasive squamous cell carcinomas of the fingernails in an AIDS patient under highly active antiretroviral therapy

Squamous cell carcinoma (SCC) of the nail unit is a rare disorder. An association with high-risk genital human papillomavirus (HPV) infection has been reported. We report a 28-year-old human immunodeficiency virus (HIV)-infected bisexual man who had multiple invasive SCC of the fingers, infected with the rare type HPV 26. Classification of HPV 26 as high- or intermediate-risk type has been uncertain, due to its rare presence in cervical cancer. Despite successful treatment with highly active antiretroviral therapy (HAART), the patient developed extensive hyperkeratotic nailbed proliferations of all fingers. Tumours were refractory to treatment and invaded into adjacent tissues. X-rays of the hands demonstrated bone invasion, necessitating amputation of distal phalanges of several fingers. Histologically, highly differentiated preinvasive and invasive verrucous SCCs were identified. Molecular DNA typing identified HPV 26 in the SCCs and in some premalignant lesions. By in situ hybridization HPV 26 DNA was detected in numerous tumour cells, indicating productive infection with high-level amplification of the viral genome. In the remaining proliferations, high-risk HPV type 58, cutaneous HPVs and a putative new HPV type were identified. HPV 26 infection appears to be causally involved in the development of SCC of the nail unit in this immunosuppressed patient. Timely evaluation of chronic verrucous nailbed tumours is recommended, especially in immunocompromised patients. Identification of HPV 26, besides known high-risk HPV types, may identify patients at risk for developing SCC of the nailbed and possibly at other locations.     

Detection of human papillomavirus DNA in squamous cell carcinomas of a patient with mycosis fungoides: report of a case

Human papillomaviruses (HPV) have been associated with squamous cell carcinomas (SCC) of the skin in both the immuno-competent and the immunocompromised individual. A paucity of literature, however, exists concerning die presence of HPV in SCCs from patients with mycosis fungoides (MF)-[cutaneous T-cell lymphoma (CTCL)]. We describe a case of multiple SCCs in which HPV DNA was detected over a 9-year period from a patient with MF. This patient with a long history of MF developed 7 small red scaly indurated lesions of sun and non-sun-exposed areas during a 9-year period (1981–1989). Histologic examination of all the lesions revealed that they were SCCs. The patient had no recorded history of arsenic exposure. To investigate the possible role of HPV as a co-carcinogen, we tested the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on formalin-fixed tissue sections using HPV L1 consensus sequence primers. Four of the 7 SCCs were positive for HPV DNA. These results suggest a possible role for HPV as a co-carcinogen in the development of SCCs in this patient.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Development of squamous cell carcinoma by two high-risk human papillomaviruses (HPVs), a novel HPV-67 and HPV-31 from bowenoid papulosis

We report a patient with bowenoid papulosis (BP) involving two high-risk human papillomaviruses (HPVs) and the development of invasive squamous cell carcinoma (SCC). Our patient showed verrucous lesions on the penis, perianal area and groin that had been noted over the previous 8 years and had recurred after all therapeutic approaches. The perianal and left inguinal lesions revealed invasive SCC on histology. HPV-31 and HPV-67 sequences were detected by polymerase chain reaction from BP lesions of the perianal area and the shaft of the penis. HPV-31 has already been reported in BP as a high-risk HPV for the development of SCC, but HPV-67 is a novel one that has never been reported in BP. As HPV-67 has sequence homology to HPV-52 and HPV-58, it belongs to the family of HPV-16, a high-risk HPV group. Thus our patient showed two high-risk HPVs, i.e. HPV-31 and the novel HPV-67, which may be directly involved in the development of SCC.     

Human papillomavirus type 58 in Bowen's disease of the elbow

Human papillomavirus (HPV) can be detected in skin lesions of Bowen's disease, particularly on the fingers, and its genotype is associated with mucosal/genital types of HPV. We report herein an 85-year-old woman who had HPV-associated Bowen's disease on her elbow. HPV-58 DNA was detected in the lesion by polymerase chain reaction with restriction fragment length polymorphism and by Southern blot hybridization. In situ hybridization revealed numerous hybrid cells in the nuclei of the upper epidermis and stratum corneum of Bowen's disease. A high-risk type of mucosal HPV-58 DNA is associated with Bowen's disease in this case, suggesting that HPV-related Bowen's disease is not always restricted to genital or finger lesions.     

Infundibular (follicular) and infundibulocystic squamous cell carcinoma: a clinicopathological and immunohistochemical study

Two types of squamous cell carcinoma (SCC), which are considered to show infundibular differentiation, have been described so far; namely, follicular SCC and infundibulocystic SCC. The latter includes (1) a well-differentiated form, (2) a less-differentiated form, and (3) an infiltrative variant. This study examined the clinicopathological features of 8 cases of SCC with infundibular differentiation, which included follicular SCCs and infundibulocystic SCCs (a less-differentiated form and an infiltrative variant). The present study confirmed that these SCCs with follicular differentiation are clinicopathologically distinct from keratoacanthoma. However, one example of infundibulocystic SCC (less-differentiated form) proved to be difficult to distinguish from keratoacanthoma. The relationship between the follicular SCC and the less-differentiated form of infundibulocystic SCC was investigated. At the periphery of the latter lesions, a focus corresponding to the follicular SCC or advanced follicular SCC lesions was seen. Therefore, these 2 types of SCCs are considered to be similar and thus represent the same neoplastic disease. The less-differentiated form of infundibulocystic SCC is considered to be a more aggressive condition. A unified term, infundibular (follicular) SCC, was used to describe these 2 conditions in this study. The clinicopathological features of the infiltrative variant of infundibulocystic SCCs were unique and distinct from the other 2 types of SCCs. This variant of infundibulocystic SCC is therefore considered to be a distinct entity and therefore has been simply called infundibulocystic SCC in this study. Infundibulocystic SCC may therefore be related to either a microcystic adnexal carcinoma or a malignant counterpart of the trichoadenoma of Nikolowski.     

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.     

Lymphatic mapping and sentinel lymphonodectomy in recurrent cutaneous squamous cell carcinomas

There are subsets of cutaneous squamous cell carcinoma (SCC), including recurrent tumours, that have a high-risk for both local recurrence and metastasis. Since the presence of regional lymph node metastases carries a poor prognosis, the early evaluation of the nodal status is crucial for staging and treatment planning. Recent trials have shown that the lymphatic mapping (LM) and sentinel lymphonodectomy (SLNE) may be successfully employed to screen nodal basins in patients with high-risk cutaneous SCCs at clinical stage N0. We report our experience with this procedure in five selected patients affected with recurrent cutaneous SCCs. A metastatic sentinel lymph node (SLN) was found in 1 of the 5 cases. No false negative result was observed. SLNE is a feasible and minimally invasive staging procedure in patients with high-risk cutaneous SCCs. It may select patients with clinically occult metastases in the regional nodal basins, who can be submitted to therapeutic lymph node dissection (LND), avoiding the morbidity of a prophylactic LND in patients without metastases in SLNs.     

Frequency and spectrum of HPV types detected in cutaneous squamous-cell carcinomas depend on the HPV detection system: a comparison of four PCR assays

BACKGROUND: The association of human papillomavirus (HPV) with cutaneous squamous-cell carcinomas (SCCs) has been described recently, but the frequency and spectrum of HPV types identified differed substantially in distinct studies. OBJECTIVE: Comparison of different PCR assays with respect to sensitivity and range of HPV types detected. METHOD: Cutaneous SCC were analyzed for HPV DNA using both consensus PCR assays with degenerate primers and PCR assays with nondegenerate primers derived from HPV types 5 and 8. RESULTS: HPV DNA was found in 50% of SCC specimens using degenerate primers. The rate of HPV-DNA-positive specimens increased to 69% when PCR assays with nondegenerate primers were applied in addition. The spectrum of HPV types detected with each of the PCR assays differed considerably. CONCLUSIONS: The frequency and spectrum of HPV types detected in cutaneous SCC strongly depends on the HPV detection system used and urges the need for standardization of HPV detection and typing in skin lesions in order to characterize HPV types predominating in distinct tumors.     

Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus

OBJECTIVES: To illustrate the potential for aggressive growth of cutaneous squamous cell carcinomas (SCCs) in patients infected with the human immunodeficiency virus (HIV) and to determine the factors associated with increased morbidity and mortality from aggressive SCCs in HIV-infected patients. DESIGN: Retrospective nonrandomized case series. SETTING: University-based dermatologic referral center. PATIENTS: A consecutive sample of 10 patients infected with HIV who had "aggressive" SCC based on the following criteria: diameter larger than 1.5 cm, rapid growth rate, local recurrence, and/or evidence of metastasis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Five patients died of metastatic SCC within 7 years of their initial diagnosis despite treatment. Human immunodeficiency virus stage and the degree of immunosuppression were not associated with increased morbidity and mortality. Patients initially undergoing combination surgery and radiation therapy or radical neck dissection had the best outcomes. CONCLUSIONS: Patients infected with HIV can develop rapidly growing cutaneous SCCs at a young age, with a high risk of local recurrence and metastasis. High-risk SCCs should be managed aggressively and not palliatively in patients infected with HIV.     

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.