Risk factors for anogenital human papillomavirus infection in men

BACKGROUND: Human papillomavirus (HPV) is strongly associated with cervical and other anogenital cancers. Identification of risk factors for HPV infection in men may improve our understanding of HPV transmission and prevention. METHODS: HPV testing for 37 types was conducted in 463 men 18-40 years old recruited from 2 US cities. The entire anogenital region and semen were sampled. A self-administered questionnaire was completed. Multivariate logistic regression aided the identification of independent risk factors for any HPV type, oncogenic HPV types, and nononcogenic HPV types. RESULTS: Prevalence was 65.4% for any HPV, 29.2% for oncogenic HPV, and 36.3% for nononcogenic HPV. Factors significantly associated with any HPV were smoking > or =10 cigarettes per day (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.3]) and lifetime number of female sex partners (FSPs) (OR for > or =21, 2.5 [95% CI, 1.3-4.6]), and factors significantly associated with oncogenic HPV were lifetime number of FSPs (OR for > or =21, 7.4 [95% CI, 3.4-16.3]) and condom use during the past 3 months (OR for more than half the time, 0.5 [95% CI, 0.3-0.8]). For nononcogenic HPV, a significant association was found for number of FSPs during the past 3 months (OR for > or =2, 2.9 [95% CI, 1.4-6.3]). CONCLUSIONS: Lifetime and recent number of FSPs, condom use, and smoking were modifiable risk factors associated with HPV infection in men.     

Epidemiologic correlates of antibody response to human papillomavirus among women at low risk of cervical cancer

A population at low risk for developing cervical cancer in Southern Brazil was studied to identify the main determinants of serological response to human papillomavirus (HPV). Enzyme-linked immunosorbent assay tests were performed in 976 women to detect serum IgG antibodies against HPV 16 L1 virus-like particles (VLPs) and HPVs 16, 18, 6 and 11 L1 VLPs as a mixture of antigens. Women with four or more sexual partners were more likely to be seropositive than women with one partner (HPV 16 serology odds ratio [OR]=3.06, 95% confidence interval [CI]: 2.0-4.8; HPV 6/11/16/18 serology OR=4.64, 95% CI: 3.0-7.2). HPV DNA and both serological responses were associated. Those positives to HPV 16 serology were twice as likely to have a cytological diagnosis of squamous intraepithelial lesions (SILs) than seronegatives (OR=2.07; 95% CI: 1.0-4.5, and OR=1.73; 95% CI: 0.8-3.8). Seropositivity to HPV 16 and HPV 6/11/16/18 antigens seem to be better markers of past sexual activity than current HPV infection, and humoral response to HPV 16 or HPV 6/11/16/18 may not be a strong indicator of cervical lesions in populations at low risk for cervical lesions.     

Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors

OBJECTIVE: To assess the prevalence of and factors associated with squamous intraepithelial lesions and condyloma [human papillomavirus (HPV)-related lesions) in HIV-infected patients. DESIGN: A cross-sectional study in a tertiary-care university hospital conducted in 516 consecutive outpatients. INTERVENTION: A systematic examination for macroscopic HPV-related lesions through anoscopy with histological confirmation, evaluation of dysplasia and HPV typing. Sexual behaviours were assessed using a semi-directive questionnaire. RESULTS: Of 473 patients examined, (200 homosexual men, 123 heterosexual men, 150 women), 108 (23%) had histologically confirmed anal HPV-related lesions (36, 15 and 11% of the respective populations), including 51 (47%) with only endoanal localization. Among these 108 patients, histological dysplasia of grades I or II and grade III were noted in 59 and two patients, respectively, invasive endoanal cancer in one; three patients also had high-risk oncogenicity HPV without dysplasia. Independent identified associated factors of HPV-related condyloma were the number of incidents of sexual intercourse per month [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01-1.06], CD4 cell count below 200 x 10 cells/l (OR 3.22; 95% CI 1.37-7.60), history of anal HPV lesion (OR 4.57; 95% CI 2.13-9.81), and receptive anal intercourse (OR 2.30; 95% CI 1.11-4.77). The two latter factors remained associated with histological dysplasia (OR 2.82; 95% CI 1.38-5.76 for history of anal condyloma, and OR 4.29; 95% CI 2.18-8.44 for receptive anal intercourse). CONCLUSION: The high rate of condyloma and histological dysplasia seen argues for a systematic screening for these lesions in HIV-infected individuals.     

Genomic polymorphism of human papillomavirus type 52 predisposes toward persistent infection in sexually active women

We investigated the role of human papillomavirus (HPV) type 52 polymorphism in the persistence of HPV infection, which is a predictor for cervical lesions. Cervical samples obtained at 6-month intervals were tested for HPV-52 in 1055 women; 41, 12, and 58 women had persistent, transient, and unclassified HPV-52 infections, respectively. HPV-52 isolates were analyzed by polymerase chain-reaction sequencing of the long control region (LCR), E6, and E7 genes. Although age (odds ratio [OR], 0.90 [95% confidence interval [CI], 0.81-0.99]), nonprototypic LCR (OR, 9.26 [95% CI, 2.1-41.7]), and E6 variant (OR, 7.04 [95% CI, 1.4-37]) were associated, in univariate analysis, with the persistence of HPV-52 infection, a nonprototypic LCR variant was the only independent predictor of it (OR, 14.1 [95% CI, 1.1-200]). In the latter variants, the loss of a binding site for a repressor of HPV expression was associated with the persistence of HPV infection (OR, 7.25 [95% CI, 1.67-31.25]).     

Human papillomavirus DNA in oral mucosal lesions

This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.     

Circumcision and human papillomavirus infection in men: a site-specific comparison

BACKGROUND: Lack of circumcision has been identified as a risk factor for male genital human papillomavirus (HPV) infection, although this association has not been consistently supported. METHODS: Specimens for HPV testing were collected from a cohort of 379 (primarily heterosexual) adult males. HPV prevalence in the glans penis and coronal sulcus, penile shaft, scrotum, semen, and urine was compared by circumcision status. RESULTS: Overall, HPV DNA prevalence ranged from 6% in semen to 52% in the penile shaft. The prevalence of any HPV infection in the glans/corona was significantly higher in uncircumcised men (46%) than in circumcised men (29%) (odds ratio [OR], 1.96 [95% confidence interval (CI), 1.02-3.75], adjusted for demographic characteristics and sexual history). Uncircumcised men also had an increased risk of oncogenic HPV infection (adjusted OR, 2.51 [95% CI, 1.11-5.69]) and infection with multiple HPV types (adjusted OR, 3.56 [95% CI, 1.50-8.50]). Among uncircumcised men, HPV prevalence in the foreskin (44%) was comparable to that in the glans/corona, and type-specific positivity was observed between the 2 sites (kappa=0.52). CONCLUSIONS: Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV, specifically localized to the glans/corona, possibly because of its proximity to the foreskin, which may be particularly vulnerable to infection.     

Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a population-based study in Costa Rica.

To examine human leukocyte antigen (HLA) involvement in the development of all grades of cervical neoplasia, a nested case-control study of 10,077 women in Guanacaste, Costa Rica, was conducted. Participants had invasive cervical cancer, high-grade squamous intraepithelial lesions (HSILs; n=166), or low-grade squamous intraepithelial lesions (LSILs); were positive for human papillomavirus (HPV) with no evidence of cervical neoplasia (n=320); or were HPV negative with no evidence of cervical neoplasia but with a history of high-risk sexual behavior (n=173). Compared with women who were HPV negative, women with HLA-DRB1*1301 were associated with decreased risk for cancer/HSILs (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) and for LSILs/HPV (OR, 0.6; 95% CI, 0.3-0.9). Women with both HLA-B*07 and HLA-DQB1*0302 had an 8.2-fold increased risk for cancer/HSILs (95% CI, 1.8-37.2) and a 5.3-fold increased risk for LSILs/HPV (95% CI, 1.2-23.7). These results support the hypothesis that multiple risk alleles are needed in order to increase risk for cervical neoplasia, but a single protective allele may be sufficient for protection.     

Human papillomavirus infection and abnormal cytology of the anus in HIV-infected and uninfected adolescents

OBJECTIVE: To examine the prevalence of and risk for anal human papillomavirus (HPV) infection and abnormal anal cytology in sexually active adolescents. DESIGN: Prevalence data from adolescents aged 13-18 years with and without HIV infection and with a history of high-risk sexual behavior. METHODS: HPV DNA was detected using amplification techniques. Abnormal anal cytology was defined as atypical squamous cell of undetermined significance or worse. RESULTS: Prevalence of anal HPV infection was similar in HIV-infected [28/58 (48%)] and uninfected [9/25 (36%)] boys (P = 0.3). but greater in HIV-infected [59/183 (59%)] than in uninfected [11/82 (13%)] girls (P < 0.001). Perianal warts were a risk for anal HPV in both boys [odds ratio (OR), 15.5; 95% confidence interval (CI), 1.6-149] and girls (OR, 9.9; 95% CI, 1.9-51.3). In subjects without anal warts, HIV infection was significant for girls (OR, 2.3; 95% CI, 1.1-4.9) and homosexual/bisexual orientation was significant for boys (OR, 5.2; 95% CI, 1.3-20.6). Abnormal anal cytology was more common among boys [32/77 (41.6%)] than girls [38/230 (16.5%)] (P < 0.001) and in addition to anal HPV, independent risk factors were positive HIV status in boys (OR, 6.5; 95% CI, 1.5-11.9) and number of partners within the past 3 months in girls (OR, 4.2; 95% CI, 1.5-11.9). CONCLUSIONS: Strong risk factors for abnormal anal cytology were HIV infection and anal HPV in boys and anal HPV and higher number of sexual partners for girls. The results suggest that anal cytology screening should be considered in HIV infected homosexual/bisexual males.     

Condylomata, cytological abnormalities and human papillomavirus infection in the anal canal in HIV-infected men

BACKGROUND: Genital infections with low-risk (LR) and high-risk (HR) human papillomavirus (HPV) genotypes are associated with ano-genital condylomata and anal squamous cell cancer. HPV-related pathologies in HIV-infected men are a serious concern. In this study, the prevalence of anal condylomata and their association with cytological abnormalities and HPV infection in the anal canal in HIV-infected men [men who have sex with men (MSM) and heterosexuals] were estimated. METHODS: This was a cross-sectional study based on the first visits of patients in the Can Ruti HIV-positive Men (CARH·MEN) cohort. Anal condylomata were assessed by clinical and proctological examination. Samples from the anal canal were collected for HPV genotyping and cytological diagnoses. RESULTS: A total of 640 HIV-infected men (473 MSM and 167 heterosexuals) were included in the study. The overall prevalence of anal condylomata was 25% [157 of 640; 95% confidence interval (CI) 21-28%]; in MSM it was 28% and in heterosexuals it was 15% [odds ratio (OR) 2.2; 95% CI 1.4-3.5]. In patients with anal condylomata, HPV infection in the anal canal was more prevalent (92% vs. 67% in those without anal condylomata; OR 8.5; 95% CI 3.2-22). This higher HPV prevalence involved at least two HPV genotypes (OR 4.0; 95% CI 2.2-7.1), mainly HR genotypes (OR 3.3; 95% CI 1.7-6.4). Similarly, the cumulative prevalence of HPV-6 and HPV-11 was higher in patients with anal condylomata (63% vs. 19% in those without anal condylomata). Having anal condylomata was associated with higher prevalences of cytological abnormalities (83% vs. 32% in those without anal condylomata; OR 6.9; 95% CI 3.8-12.7) and high-grade squamous intraepithelial lesions (HSILs) (9% vs. 3% in those without anal condylomata; OR 9.0; 95% CI 2.9-28.4) in the anal canal. CONCLUSIONS: HIV-infected men with anal condylomata were at risk of presenting HSILs and harbouring multiple HR HPV infections in the anal canal. Although MSM presented the highest prevalence of anal condylomata, heterosexual men also had a clinically important prevalence. Our findings emphasize the importance of screening and follow-up for condylomata in the anal canal in HIV-infected men.     

Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2 infections

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women.     

Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear

The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa kappa = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.     

Tumor immune escape by the loss of homeostatic chemokine expression

The novel keratinocyte-specific chemokine CCL27 plays a critical role in the organization of skin-associated immune responses by regulating T cell homing under homeostatic and inflammatory conditions. Here we demonstrate that human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. Compared with healthy skin, CCL27 mRNA and protein expression was progressively lost in transformed keratinocytes of actinic keratoses and basal and squamous cell carcinomas. In vivo, precancerous skin lesions as well as cutaneous carcinomas showed significantly elevated levels of phosphorylated ERK compared with normal skin, suggesting the activation of EGFR-Ras signaling pathways in keratinocyte-derived malignancies. In vitro, exogenous stimulation of the EGFR-Ras signaling pathway through EGF or transfection of the dominant-active form of the Ras oncogene (H-RasV12) suppressed whereas an EGFR tyrosine kinase inhibitor increased CCL27 mRNA and protein production in keratinocytes. In mice, neutralization of CCL27 led to decreased leukocyte recruitment to cutaneous tumor sites and significantly enhanced primary tumor growth. Collectively, our data identify a mechanism of skin tumors to evade host antitumor immune responses.     

Human papillomavirus DNA in cutaneous primary and metastasized squamous cell carcinomas from patients with epidermodysplasia verruciformis.

DNA extracted from squamous cell carcinomas from patients with the chronic wart disease syndrome, epidermodysplasia verruciformis, was analyzed for the presence of human papillomavirus (HPV)-specific DNA sequences by Southern blot hybridization analysis. Employing an HPV probe obtained by molecular cloning of viral DNA purified from benign warts from these patients, we have unequivocally identified HPV-specific nucleotide sequences in squamous cell carcinomas from these patients. Restriction endonuclease mapping indicated that the DNA present in the carcinomas was of the same type (type 5) as that found in the benign tumors from these patients and was present as unintegrated, free viral DNA. Moreover, we have demonstrated the presence of HPV-5 DNA in a subcutaneous metastatic tumor from one of these patients. This latter observation essentially eliminates the possibility that the HPV-5 DNA present in the malignant tumors in these patients resulted from cross-contamination from an adjacent benign warty lesion. In addition to wild-type HPV-5 DNA, both the primary and metastatic carcinomas analyzed also contained an HPV-5 DNA species lacking approximately 20% of the HPV-5 DNA genome. These subgenomic forms of HPV-5 DNA could not be detected in benign papillomas from these patients.     

Human papillomavirus type 33 polymorphisms and high-grade squamous intraepithelial lesions of the uterine cervix

BACKGROUND: We investigated the association between polymorphisms of human papillomavirus (HPV)-33 and squamous intraepithelial lesions (SILs). METHODS: Endocervical specimens from 89 women infected with HPV-33, out of a total of 5347 recruited for 2 case-control and 2 cohort studies, were further analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS: Of the 89 samples, 64 were normal, 7 had low-grade SILs (including 3 determined by histopathologic analysis), 15 had high-grade SILs (HSILs, including 14 determined by histopathologic analysis), and 3 had an unknown diagnosis. Non-prototype-like LCR variants were significantly associated with HSILs (age- and study site-adjusted odds ratio [OR], 9.2 [95% confidence interval {CI}, 1.8-45.9]). The C7732G variation, which results in the loss of a putative binding site for the cellular upstream stimulatory factor, was associated with HSILs (age- and site-adjusted OR, 8.0 [95% CI, 1.5-42.8]). E6 and E7 polymorphisms were not associated with HSILs. Samples collected at 6-month intervals from 14 participants contained the same variant. The HPV-33 MT 1-0-0 variant carrying the G7584A variation was detected more frequently in women from Brazil (7/20 [35%]) than in women from Canada (1/65 [1.5%]; P=.001). CONCLUSION: Intratypic LCR variants of HPV-33 seem to vary geographically and to differ with respect to their oncogenic potential.     

High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV

OBJECTIVE: To examine associations between levels of episomal and integrated human papillomavirus (HPV) 16 DNA and the grade of cervical disease. DESIGN: Cross-sectional data were obtained from a cohort of women with and without HIV infection and with high-risk sexual behaviour. METHODS: Episomal and integrated HPV-16 DNA loads were measured in cervicovaginal lavages collected from 75 women (58 HIV seropositive, 17 HIV seronegative) using real-time polymerase chain reaction assays, controlling for cell content and the presence of inhibitors. RESULTS: HPV-16 viral loads were significantly higher in women with high-grade squamous intraepithelial lesions (n = 6) than in women with normal cytology (n = 44), whether total (10(8.28) versus 10(5.10) HPV-16 DNA copies/microg DNA), episomal (10(7.99) versus 10(4.61)) or integrated (10(7.95) versus 10(4.77)) HPV-16 viral loads were measured (P < 0.02 for each comparison). Thirty-nine women had colposcopy [11 normal cervix, 16 cervical intraepithelial neoplasia (CIN) 1, six CIN 2, six CIN 3] and 24 additional women had three consecutive normal cytology smears. Controlling for age, race, CD4 cell count and HIV status, total (OR 3.5, 95% CI 1.2-10.4; P = 0.02), episomal (OR 2.9, 95% CI 1.2-7.4; P = 0.02,) and integrated (OR 1.6, 95% CI 1-2.6; P = 0.05) HPV-16 DNA loads were significantly associated with CIN 2,3, but the differences between CIN 1 and CIN 2,3 were not significant (P > 0.06). A greater amount of cellular DNA was collected from women with CIN 2,3 (P = 0.007). CONCLUSION: Higher HPV-16 DNA loads are associated with cervical lesions detected by either histology or cytology. No additional information is gained by measuring integrated or episomal over total HPV-16 DNA loads.     

Human papillomavirus (HPV) type 6 and 16 DNA sequences in bronchial squamous cell carcinomas demonstrated by in situ DNA hybridization

A series of 131 routinely processed, paraffin-embedded biopsy specimens derived from the same number of patients with a bronchial squamous cell carcinoma were analyzed using in situ DNA-hybridization technique with a probe cocktail containing³⁵S-labeled human papillomavirus (HPV) DNA of types 6, 11, 16, 18, and 30. The 12 carcinomas shown to contain HPV DNA by the probe cocktail were subjected to in situ hybridization with the specific HPV DNA probes applied separately under high stringency conditions. HPV DNA could be found in 9 of these carcinomas; 2 cases contained HPV 6 DNA and 7 hybridized with HPV 16 DNA. The role of HPV in the development of bronchial squamous cell carcinoma is discussed in the light of the previously established morphologic evidence as well as the increasing number of reports on malignant transformation of the respiratory tract HPV lesions. The present findings of HPV DNA sequences provide further support to the concept of HPV as a potential causative agent of some bronchial squamous cell carcinomas, possibly acting synergistically with chemical or physical carcinogens. As in the genital tract, it seems clear that a respiratory tract infection by “low-risk” HPV types 6 and 11 by no means excludes the possibility of malignancy, so far ascribed almost exclusively to the “high-risk” type HPV 16.     

Dermatologic lesions and risk for cancer

There are three major types of skin cancer. Basal cell carcinoma and squamous cell carcinoma are both carcinomas from epithelial cells, whereas melanoma originates from the melanocytes of the skin. Although these skin cancers can develop without precursors, there are some skin lesions which may give rise to malignancies. In chronological order, we discuss the (potential) precancerous lesions of basal cell carcinoma (sebaceous nevus), squamous cell carcinoma (chronic inflammation, actinic keratosis, kerato-acanthoma, Bowen's disease, leukoplakia, and lichen sclerosus) and malignant melanoma (lentigo maligna and dysplastic naevi).     

Anal cancer in Chinese: human papillomavirus infection and altered expression of p53

ＡｎａｌｃａｎｃｅｒｉｎＣｈｉｎｅｓｅ：ｈｕｍａｎｐａｐｉｌｏｍａｖｉｒｕｓｉｎｆｅｃｔｉｏｎａｎｄａｌｔｅｒｅｄｅｘｐｒｅｓｓｉｏｎｏｆｐ５３ＬＡＩＭａｏＤｅ,ＬＵＯＭｉｎＪｉｅ,ＹＡＯＪｉａｎＥｒａｎｄＣＨＥＮＰｅｉＨｕｉＳｕｂｊｅｃｔ...     

Anal cancer in Chinese: human papillomavirus infection and altered expression of p53

AIM To detect the presence of HPV DNA and study the alteration of p53 expression in anal cancers in Chinese.METHODS HPV DNA was amplified by PCR. The amplified HPV DNA was classified by DBH. HPV antigen and p53 expression were respectively detected by immunohistochemistry.RESULTS HPV DNA was amplified only in one case of squamous cell carcinoma of the 72 Chinese anal cancers and further classified as HPV type 16. Others were all HPV negative. HPV antigen and p53 expression were also detected in this case. Positive stainings with anti-p53 antibody were seen in 61.2% anal cancers. There were no statistically significant differences between anal squamous cell carcinomas and adenocarcinomas and between anal adenocarcinomas and rectal adenocarcinomas. p53 protein expression was observed in the basal cells of squamous epithelium of condyloma acuminatum and morphologically normal squamous epithelium in 2 cases invaded by anal adenocarcinoma.CONCLUSION HPV infection was not associated with these cases of anal cancer. p53 alteration was a common event. Positive p53 immunostaining can not be regarded as a marker for differentiating benign from malignant lesions.     

Risk factors for squamous intraepithelial lesions in systemic lupus erythematosus: a prospective cohort study

Objective

We undertook a prospective cohort study to ascertain the risk factors for the development of squamous intraepithelial lesions (SIL) in patients with systemic lupus erythematosus (SLE).

Methods

One hundred thirty‐seven SLE patients with a normal Papanicolaou (Pap) smear at baseline were evaluated at 6‐month intervals for up to 3 years. At each visit, a Pap smear, human papillomavirus (HPV) DNA test, and clinical assessment were performed.

Results

Among the 137 patients, there were 12 incident cases (8.8%) of SIL over a median followup duration of 30.7 months (interquartile range 25.5–31.7). Among the 30 patients with HPV infection detectable by DNA testing at baseline, 9 (30%) developed SIL. The independent risk factors for the incident SIL in this group of SLE patients included the use of cyclophosphamide (CYC) ever (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 1.1–29.3; P = 0.041) and persistent high‐risk HPV infection (OR 26.9, 95% CI 3.2–222.3; P = 0.002). The use of baseline HPV testing has a higher sensitivity than abnormal cytology (defined as atypical squamous cells of undetermined significance; 47.7% versus 33.3%) in predicting the development of SIL.

Conclusion

Independent risk factors associated with the development of SIL in SLE patients included persistent high‐risk HPV infection and the use of CYC. Low‐risk patients who receive negative test results on both cervical cytology screening and HPV DNA testing may not need to be rescreened within 3 years.