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Objectives: While Mycoplasma genitalium is reported as a common rectal infection among men who have sex with men (MSM), published data refer predominantly to urethral infections. Currently, most guidelines recommend M. genitalium testing from urine in men with symptomatic, non-gonococcal urethritis. Macrolide resistance-associated mutations (MRMs) among M. genitalium have increased during the last decade especially among MSM. We aim to demonstrate the prevalence and anatomical distribution of M. genitalium infection and MRM in urine and rectal specimens among MSM in Sweden., Methods: In this cross-sectional study in 2019, paired urine and rectal samples from symptomatic and asymptomatic MSM attending a sexually transmitted infection clinic in the south of Sweden were screened for M. genitalium , presence of MRM, Neisseria gonorrhoeae , Chlamydia trachomatis , HIV and syphilis., Results: The overall prevalence of M. genitalium was 10.5% (64 of 609), rectal samples 7.6% (46 of 609) and urine samples 3.9% (24 of 609) (p=0.007). Among M. genitalium -positive cases, single rectal and single urethral infection was detected in 62.5% (40 of 64) and 28.1% (18 of 64), respectively (p<0.0001). Infection at both sites was seen in 9.4% (6 of 64). The prevalence of MRM was 67.9% (19 of 28). M. genitalium was significantly associated with HIV (OR 2.60, 95% CI 1.14 to 5.88, p=0.02). Among the MSM, 7.4% (45 of 609) were infected with N. gonorrhoeae, 6.7% (41 of 609) with C. trachomatis , 7.1% (43 of 609) with HIV and 0.7% (4 of 609) with syphilis., Conclusions: In this study, among MSM, most infections with M. genitalium were detected as rectal mono infections. The prevalence of M. genitalium among MSM was almost twofold higher in rectal samples (7.6%) compared with urine samples (3.9%). The prevalence of macrolide resistance was high with no difference between urine and rectal samples., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Primary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30-70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow-up of women with cervical dysplasia., Material and Methods: We performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017-2020., Results: We identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017-2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings., Conclusions: The most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objectives: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years., Materials and Methods: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population., Results: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24)., Conclusions: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To investigate the prevalence of pathological disease and spectrum of human papillomavirus (HPV) types among symptomatic foreskin tissue., Patients and Methods: Consecutively excised symptomatic foreskins from 351 men were sent for histopathological evaluation. During the surgical procedure, a fresh biopsy was taken for HPV analysis by modified general primer polymerase chain reaction. A medical questionnaire regarding medication, smoking habits, number of lifetime sexual partners, former diseases and surgery performed on penis was completed by all participants., Results: The most common clinical diagnosis and cause for circumcision was phimosis, seen in 85.2%. Histopathologically inflammatory dermatological conditions were present in 87% of the men. The most common histopathological diagnosis was lichen sclerosus (LS) observed among 58.7%. Notably, penile intraepithelial neoplasia (PeIN) was present in 2% without former clinical suspicion. Overall, HPV was detected in 17.1% of the men and 28 different HPV types were found. High-risk (HR) HPV types were identified in 9.1% and HPV16 was present in 2.3%. Current smoking increased the risk of HPV (crude odds ratio [OR] 2.8, confidence interval [CI] 1.4-5.6; P = 0.005). Having >15 lifetime sexual partners increased the risk of HPV (crude OR 2.6, 95% CI 1.4-5.1; P = 0.003) and when adjusted for current smoking the OR was substantially increased (OR 6.0, 95% CI CI 2.2-16.8; P < 0001)., Conclusions: Histopathological evaluation of circumcised symptomatic foreskin revealed PeIN in 2% of the men without any clinical suspicion of malignancy and that treatable dermatological conditions were present in 87%, LS being the most common. HR-HPV types were present in 9%. Due to risk of malignant development both in PeIN and in inflammatory skin diseases we recommend sending all excised foreskins from patients with symptoms for histopathological evaluation as guidance for further clinical management., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: During 2013 and 2016 the region of Skåne, Sweden started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate high-risk (HR) HPV mRNA testing for the triage of HPV DNA-positive postmenopausal women with normal cytology., Methods: A total of 271 women, 60-65 years of age, underwent liquid-based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic Inc.). Over a period of 49 months (SD 11.0) the women received regular follow-ups at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV DNA and/or mRNA result at two subsequent visits were scheduled for colposcopy and clinical examination., Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA-positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse. The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.5% 107/271) and 0% among HPV mRNA-negative women (60.5%, 164/271), (p = 0.002)., Conclusions: Postmenopausal women with normal cytology testing positive for HR-HPV mRNA are at increased risk for the development of high-grade cervical intraepithelial neoplasia (CIN), in contrast to women with a negative HR-HPV mRNA outcome. The HR-HPV mRNA APTIMA assay detecting 14 HR-HPV types may be a useful triage method among HPV DNA-positive postmenopausal women with normal cytology.

High-grade serous ovarian cancer (HGSOC) is the most common subtype of epithelial ovarian cancer and early detection is challenging. TP53 mutations are a hallmark of HGSOC and detection of these mutations in liquid-based Pap samples could provide a method for early diagnosis. Here we evaluate the use of IBSAFE, an ultra-sensitive droplet digital PCR (ddPCR) method, for detecting TP53 mutations in liquid-based Pap samples collected from fifteen women at the time of diagnosis (diagnostic samples) and/or up to seven years prior to diagnosis (archival samples). We analysed tumours for somatic TP53 mutations with next generation sequencing and were able to detect the corresponding mutations in diagnostic samples from six of eight women, while one patient harboured a germline mutation. We further detected a mutation in an archival sample obtained 20 months prior to the ovarian cancer diagnosis. The custom designed IBSAFE assays detected minor allele frequencies (MAFs) with very high assay sensitivity (MAF = 0.0068%) and were successful despite low DNA abundance (0.17-206.14 ng, median: 17.27 ng). These results provide support for further evaluation of archival liquid-based Pap samples for diagnostic purposes and demonstrate that ultra-sensitive ddPCR should be evaluated for ovarian cancer screening in high-risk groups or in the recurrent setting.

Primary HPV screening for cervical cancer by HPV mRNA testing (Aptima) was implemented in January 2017, for women ≥30 through 70 years, in the Region of Skåne, Sweden. HPV positive samples underwent cytology assessment, and women with any degree of abnormal cytology were referred for colposcopy. The aim was to audit the primary HPV screening program, by comparing the cytology results to those of corresponding women (aged ≥30 through 65 years) screened with conventional cytology during 2016. Overall, HPV was detected among 7.0% (4433/63,055) of the women ≥30-70 years in the primary HPV screening program. Among a co-tested (cytology and HPV) subgroup aged 40-42 years (N = 5039), HPV was detected in 100% (28/28) of high-grade squamous intraepithelial lesions (HSIL) and atypical squamous cells of undetermined significance (ASCUS) where HSIL could not be excluded (ASCH) (9/9), and in 80% (4/5) of cases of atypical glandular cells (AGC). Among women ≥30-65 years, the proportion ASCUS or worse (ASCUS+) was similar with cytology (3.52% [2016]) and primary HPV screening (3.70% [2017]). Only the proportion of ASC-H changed by the use of primary HPV screening, from 0.13% (2016) to 0.23% (2017) (p < 0.001). The colposcopy referral rate increased by 54% (3.70 vs 2.41%), when primary HPV screening was introduced. In conclusion, the implemented primary HPV screening approach demonstrated similar prevalence of ASCUS+ cytology as conventional screening. In addition, primary HPV screening decreased cytology assessments by 86% in our screening population of women 30 through 70 years taken into account the co-tested women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.

Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at -80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5-7 years later were comparable [76.3% (95% CI: 65.8%-84.3%) and 82.5% (95% CI: 72.6%-89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95-99.98) and 99.98% (95% CI: 99.96-99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening., (© 2018 UICC.)

Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74 % of the HPV-positive cases. HPV was detected in 65 % (92/141) and 11 % (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73 % (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003-1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100 % (17/17) and 68 % (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6 %, whereas entirely episomal and mixed virus was detected in 51 and 42 % of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48 %), the episomal HPV16 is salient (93 %) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.

Papillomaviruses (PV) are a remarkably heterogeneous family of small DNA viruses that infect a wide variety of vertebrate species and are aetiologically linked with the development of various neoplastic changes of the skin and mucosal epithelia. Based on nucleotide similarity, PVs are hierarchically classified into genera, species and types. Novel human PV (HPV) types are given a unique number only after the whole genome has been cloned and deposited with the International HPV Reference Center. As of 9 March 2015, 200 different HPV types, belonging to 49 species, had been recognized by the International HPV Reference Center. In addition, 131 animal PV types identified from 66 different animal species exist. Recent advances in molecular techniques have resulted in an explosive increase in the identification of novel HPV types and novel subgenomic HPV sequences in the last few years. Among PV genera, the γ-PV genus has been growing most rapidly in recent years with 80 completely sequenced HPV types, followed by α-PV and β-PV genera that have 65 and 51 recognized HPV types, respectively. We reviewed in detail the contemporary molecular methods most often used for identification and characterization of novel PV types, including PCR, rolling circle amplification and next-generation sequencing. Furthermore, we present a short overview of 12 and 10 novel HPV types recently identified in Sweden and Slovenia, respectively. Finally, an update on the International Human Papillomavirus Reference Center is provided., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Many cervical cancers occur among women who have not attended cervical screening. Strategies to reach non-attending women may improve the effectiveness of cervical screening programmes., Objective: To compare the responses among long-term non-attending women to either (i) HPV-testing of a self-collected vaginal sample, or (ii) cytological screening with a flexible no-fee appointment for sampling at an outpatient clinic., Study Design: Among the 242,000 women aged 32-65 years in Southern Sweden, we identified 28,635 women who had not had any cervical smears taken for >9 years. We randomized 1000 women to invitation to HPV self-sampling, and 500 women to flexible outpatient clinic appointments. Responding women received a questionnaire about their reasons for previous non-attendance., Results: The response rate to HPV self-sampling was three times higher than the flexible outpatient clinic invitations (147/1000 women (14.7%) compared to 21/500 (4.2%) p<0.0001). High-risk (hr)-HPV was found in 10/147 self-sampled women (6.9%). 7/10 hr-HPV-positive women attended colposcopy, but no HSIL was found. Among the clinic-sampled women, 2/21 had hr-HPV and 1/21 had HSIL. Reasons for not attending were "uncomfortable with vaginal examination", "feel healthy", "lack of time" and "experience of unfriendly health workers"., Conclusions: Although the response rate was low for both interventions, the invitation to vaginal HPV self-sampling was more effective for increasing the coverage of the screening programme. The fact that "uncomfortable with vaginal examination" was the most common reason for non-attending suggests that self-sampling could be further explored as a strategy to increase the coverage of cervical screening programmes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Whereas the antibody response to the anogenital human papillomaviruses (HPVs) is known to be mainly type-specific, correlated with the presence of viral DNA and mainly directed to conformational epitopes of the virion, it is not known if this applies also to the antibody response to cutaneous HPVs. For 434 non-immunosuppressed patients with skin lesions (squamous cell carcinoma and basal cell carcinoma of the skin, actinic keratosis and benign skin lesions), we compared HPV DNA status with seroreactivity to HPV pseudovirions (PsV) and to GST-L1 fusion proteins from HPV types -5, -6, -15, -16, -32 and -38. Biopsies from the skin lesions were tested for the presence of HPV DNA using three different PCR methods, with typing by sequencing. Serum samples from subjects with HPV DNA-positive biopsies and randomly selected serum samples from subjects with HPV DNA-negative biopsies were also tested with neutralization assays with HPV5, -38 and -76 PsV. Agreement of the three serological methods varied from poor to moderate. Type-specific seroprevalences among patients positive for the same type of HPV DNA (sensitivity of serology) was improved with the PsV-based method (mean of 40%, maximum 63%) compared with the GST-L1 method (mean of 20%, maximum of 25%). Neutralization was the most sensitive assay for HPV38 (50%). In summary, cutaneous HPVs also appear to induce a type-specific antibody response that correlates with the presence of HPV DNA and that can be detected with improved sensitivity using PsV-based serology.

Background: Monitoring of condylomas is an early evidence of population effectiveness of human papillomavirus (HPV) vaccination programs. If reporting could include HPV typing, the contribution by vaccine HPV types to condyloma burden could be monitored., Methods: A sentinel site for reporting of condyloma including HPV typing was established at the Centre for Sexual Health in Malmö, Sweden. In 2006 to 2009, when there were few HPV vaccines, 621 subjects with condyloma were reported and HPV genotyped., Results: Ninety-four percent of the condylomas contained genital HPV types. Thirty-five different genital HPV types were identified, with HPV6 (62%), HPV16 (13%), and HPV11 (10%) being the most common. At least 1 of the 4 HPV types in the HPV6/11/16/18 vaccine was detected in 77%. High-risk HPV types were more common in females (45%) than among males (27%) (odds ratio, 1.9; confidence interval, 1.3-2.8). Extended testing among subjects initially negative for HPV found 21 patients with cutaneous types of HPV, including a novel type (HPV153)., Conclusions: This report provides a baseline distribution of HPV types in condylomas before the introduction of an HPV vaccination program in this population. Human papillomavirus typing is feasible in routine condyloma reporting.

Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell carcinoma (SCC) in case-control studies, but there are limited data from prospective studies assessing whether virus exposure predicts risk of future cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from 850,000 donors, were searched for incident skin cancer for up to 30 years using registry linkages. Altogether, 2,623 donors with samples taken before diagnosis of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic samples and samples from 2,623 matched controls were tested for antibodies against 33 types of HPV. Baseline seropositivity to HPV types in genus β species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.7); this was also the case for samples taken more than 18 years before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type-specific persistent seropositivity entailed elevated point estimates for SCC risk for 29 HPV types and decreased point estimates for only 3 types. After multiple hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV 9 with BCC risk. In summary, seropositivity for certain HPV types was associated with an increased risk for future development of SCC and BCC.

Background: Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective., Methods: We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided., Results: Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests)., Conclusions: Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy., (Copyright 2002 Wiley-Liss, Inc.)

The polymerase chain reaction (PCR) was used to investigate samples from Indonesian and Swedish patients with cervical intraepithelial neoplasia grade III (CIN III), squamous cell carcinoma or adenocarcinoma of the cervix for the presence of a transforming fragment (BC 24) of herpes simplex virus type 2 (HSV-2) DNA. The PCR test for HSV-2 DNA was more sensitive than the infectivity endpoint titer in a cell culture system and no cross reactivity was found with either varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human papillomavirus 16 or 18, or human genomic DNA. Using this PCR test, 2 out of 5 cases with CIN III, 10 of 71 squamous cell carcinomas, and 3 of 11 adenocarcinomas of the uterine cervix were found to contain DNA sequences homologous to the BC 24 fragment of the HSV-2 genome. Only two of the samples containing this transforming region of the HSV-2 DNA were positive in a PCR assay for the HSV-2 DNA polymerase gene. The great majority of the HSV-2 BC 24 DNA positive (12 of 15) came from the Indonesian group of patients. All 15 CIN III or cancer samples positive for the HSV-2 BC 24 fragment were also positive for papillomavirus DNA. In line with observations made by others, our data support the hypothesis that HSV infection could represent one of several possible oncogenic cofactors leading to cervical carcinoma. The HSV cofactor might be more important in the Indonesian than in the Swedish population.