Bengt-Göran Hansson

Efficacy of HPV DNA Testing With Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening

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.

Clinical aspects of delta infection.

The clinical features of delta infection were analysed retrospectively in 191 hepatitis B surface antigen (HBsAg) carriers and 592 cases of acute hepatitis B seen over 11 years in the Swedish town of Malmö (population 250 000). With a few exceptions delta infections occurred exclusively in drug addicts. In the chronic HBsAg-carriers the most common clinical manifestation was an episode of acute hepatitis, which in some individuals became severe with a pronounced rise in serum alanine aminotransferase activity for many months. During the period of delta infection the HBsAg titre was lowered and in three out of 26 cases the patient lost HBsAg altogether and developed hepatitis B surface antibodies (anti-HBs). In one patient the acute hepatitis due to delta infection was fulminant and fatal. In patients with acute hepatitis B the clinical picture did not distinguish between those with and without simultaneous delta infection. The frequency with which acute hepatitis B was succeeded by a chronic carrier state was the same whether or not the patient was infected simultaneously with the delta agent. The discovery of the delta agent has improved understanding of the natural history of chronic hepatitis B infection in drug addicts. Thus, instances of acute hepatitis in a chronic carrier, previously termed hepatitis non-A, non-B, may actually be episodes of delta infection.

HPV type-specific risks of high-grade CIN during 4 years of follow-up: A population-based prospective study

We followed a population-based cohort of 5696 women, 32–38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.

Increased occurrence of hepatitis A with cyclic outbreaks among drug addicts in a Swedish community

SummaryTo determine the prevalence of antibodies toHepatitis A virus (anti-HAV) among drug addicts, sera collected in a Swedish city during a ten-year period from 234 drug addicts with acute hepatitis B were tested for anti-HAV. The results were compared with the normal population, where only 3.8% of those born after 1950 were anti-HAV-positive. In individuals born between 1941 and 1965, 8.2% in the normal population and 30.2% of the drug addicts were anti-HAV-positive (p<0.001). The level of immunity to hepatitis A among drug addicts ranged from 7.7% to 60% during the ten-year period. Low levels of immunity were seen in the years preceeding outbreaks of hepatitis A among drug addicts. These outbreaks occurred in a cyclic pattern. Higher levels of immunity were seen after each outbreak.ZusammenfassungZur Bestimmung der Prävalenz vonHepatitis A Virus-Antikörpern (anti-HAV) bei Drogenabhängigen wurden Seren von 234 Drogenabhängigen mit akuter Hepatitis B, die in einer schwedischen Stadt während zehn Jahren gesammelt worden waren, auf anti-HAV getestet. Zum Vergleich wurde eine normale Bevölkerungsgruppe herangezogen, bei der nur 3,8% der nach 1950 Geborenen und 8,2% der Jahrgänge 1941–1965 anti-HAV positiv waren. Hingegen war bei 30,2% der Drogenabhängigen anti-HAV nachzuweisen (p<0,001). Die Rate von Drogenabhängigen mit Immunschutz variierte innerhalb von zehn Jahren zwischen 7,7% und 60%. In den Jahren von Hepatitis A-Ausbrüchen waren die Immunitätsraten jeweils niedrig. Die Ausbrüche traten zyklisch auf. Nach jedem Ausbruch war jeweils eine höhere Rate von Drogensüchtigen mit Immunschutz festzustellen.To determine the prevalence of antibodies toHepatitis A virus (anti-HAV) among drug addicts, sera collected in a Swedish city during a ten-year period from 234 drug addicts with acute hepatitis B were tested for anti-HAV. The results were compared with the normal population, where only 3.8% of those born after 1950 were anti-HAV-positive. In individuals born between 1941 and 1965, 8.2% in the normal population and 30.2% of the drug addicts were anti-HAV-positive (p<0.001). The level of immunity to hepatitis A among drug addicts ranged from 7.7% to 60% during the ten-year period. Low levels of immunity were seen in the years preceeding outbreaks of hepatitis A among drug addicts. These outbreaks occurred in a cyclic pattern. Higher levels of immunity were seen after each outbreak. Zur Bestimmung der Prävalenz vonHepatitis A Virus-Antikörpern (anti-HAV) bei Drogenabhängigen wurden Seren von 234 Drogenabhängigen mit akuter Hepatitis B, die in einer schwedischen Stadt während zehn Jahren gesammelt worden waren, auf anti-HAV getestet. Zum Vergleich wurde eine normale Bevölkerungsgruppe herangezogen, bei der nur 3,8% der nach 1950 Geborenen und 8,2% der Jahrgänge 1941–1965 anti-HAV positiv waren. Hingegen war bei 30,2% der Drogenabhängigen anti-HAV nachzuweisen (p<0,001). Die Rate von Drogenabhängigen mit Immunschutz variierte innerhalb von zehn Jahren zwischen 7,7% und 60%. In den Jahren von Hepatitis A-Ausbrüchen waren die Immunitätsraten jeweils niedrig. Die Ausbrüche traten zyklisch auf. Nach jedem Ausbruch war jeweils eine höhere Rate von Drogensüchtigen mit Immunschutz festzustellen.

Human papillomavirus typing in reporting of condyloma.

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.

Antibody to a hepatitis C virus related protein among patients at high risk for hepatitis B

Anti-HCV prevalence in treated hemophiliacs, their heterosexual partners, intravenous drug addicts and homosexual men was studied. In hemophiliacs and many of the intravenous drug addicts, greater than or equal to 2 sera drawn 1-18 or 1-17 years apart were available. Anti-HCV testing was performed by ELISA (Ortho). Among patients with severe and moderate hemophilia A, 87% (98/112) were positive for anti-HCV at least once and among patients with severe and moderate hemophilia B, 83% (24/29) were positive for anti-HCV. Seroconversion to anti-HCV was observed in 21% of hemophilia patients. In hemophilia A, HCV infection generally occurred during the first years of life and in hemophilia B somewhat later. Loss of anti-HCV antibody was seen in 12% (17 patients). The rest, 54% (76 patients) were seropositive in first and last samples. All 12 tested spouses to anti-HCV positive men were anti-HCV negative. 80% of the drug addicts (137/172) were seropositive for anti-HCV. In those with greater than 1 serum tested, 8% were consistently negative and 68% consistently positive. 21% seroconverted to anti-HCV while 3% lost antibody. 10% (22/211) of homosexual men were anti-HCV positive. Intravenous transmission of HCV thus seemed highly efficient whereas sexual transmission was much less efficient.

Relation between donor transaminase and recipient hepatitis non-A, non-B in Sweden

Abstract. The relation between donor alanine aminotransferase (ALT) and recipient post‐transfusion hepatitis (PTH) non‐A, non‐B was studied in patients tested before and 6 and 12 weeks after transfusion. The minimum ALT criterion for PTH was 105 IU/1 (> 2.5 times the upper normal of 42 IU/1). In 8.8% of donors, ALT was > 42 IU/1, and in 2.3% ALT was > 63 IU/1, i.e., 1.5 times elevated. PTH non‐A, non‐B occurred in 14 of 742 recipients. The PTH incidence increased when donor ALT was above 63 IU/1 (1.5 vs. 5.6%; p < 0.05). However, if the confounding factor of volume variations was compensated for, elevated donor ALT and PTH were only statistically linked among recipients < 70 years (p < 0.02; Mantel‐Haenszel test).

Improved technique for detecting Australia antigen by immunoelectroosmophoresis.

Abstract. Comparison between the sensitivity in detecting Australia antigen of the Ouchterlony double diffusion method and the immunoelectroosmophoresis (IEOP) was made. The IEOP technique using pure agarose and staining the plates was 21 times more sensitive than the Ouchterlony method. In cases of hepatitis it was possible to detect Australia antigen for 50% longer time with IEOP than with the Ouchterlony method. The practical application of IEOP for detection of Australia antigen and antibodies is discussed.

HIV seroconversion in Swedish haemophiliacs: relation to type and dosage of factor concentrate

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat‐treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non‐heat‐treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.

Antibody to Hepatitis-C-Virus-Related Proteins in Sera from Alanine-Aminotransferase-Screened Blood Donors and Prospectively Studied Recipients

Abstract. A prospective study of posttransfusion non‐A, non‐B hepatitis was conducted in Malmö, Sweden, in 1984–1985, in which donors were alanine aminotransferase (ALT) screened but not ALT selected. Among 741 patients studied at 0, 6, and 12 weeks after transfusion, 13 developed non‐A, non‐B hepatitis, and these were further followed up. Stored sera from the 13 hepatitis patients and their 123 donors were tested for anti‐hepatitis C virus (HCV) by ELISA and, if positive, analyzed by recombinant immunoblot assay (RIBA). All ALT‐elevated blood units (n = 301) and a similar number of ALT‐normal units were also tested. Only 4/13 patients with non‐A, non‐B hepatitis seroconverted to anti‐HCV, all with ALT peaks >10 times the upper normal. All seroconversions occurred within 5 months after transfusion and could be confirmed by RIBA. Hepatitis C in recipients occurred both after transfusion of blood that was strongly positive, weakly positive, and/or negative for anti‐HCV by ELISA. In donors grouped by ALT levels, the anti‐HCV prevalence varied between 0.4 (normal ALT) and 14% (ALT elevated ≥ 2 times). Of the total of 9 donor units positive by ELISA, only 5 were confirmed by RIBA. Of the 5 recipients of the RIBA‐positive blood units, 3 went into hepatitis, 1 remained normal at 10.5 weeks, and 1 showed a slight, transient ALT elevation at week 12. The recipients of ELISA‐positive but RIBA‐negative blood remained healthy.