Clinical value of fully automated p16/Ki-67 dual staining in the triage of HPV-positive women in the Norwegian Cervical Cancer Screening Program.

BACKGROUND: More accurate biomarkers in cervical cytology screening could reduce the number of women unnecessarily referred for biopsy. This study investigated the ability of p16/Ki-67 dual staining to predict high-grade cervical intraepithelial neoplasia (CIN) in human papillomavirus (HPV)-positive women from the Norwegian Cervical Cancer Screening Program. METHODS: Automated p16/Ki-67 dual staining was performed on liquid-based cytology samples from 266 women who were HPV-positive at their secondary screening. At a mean of 184 days after p16/Ki-67 staining, 201 women had a valid staining result and a conclusive follow-up diagnosis (histological diagnosis or HPV-negative diagnosis with normal cytology findings). The sensitivity and specificity for predicting the follow-up diagnosis were compared for cytology, p16/Ki-67 dual staining, and their combination. RESULTS: Sixty-seven percent of the study sample was p16/Ki-67-positive. The sensitivity of p16/Ki-67 staining for predicting CIN-2/3 was statistically significantly higher than the sensitivity of cytology (0.88 vs 0.79; P = .008), but this was not true for the prediction of CIN-3 (0.94 vs 0.88; P = .23). The specificity of cytology for predicting CIN-3 was significantly higher than the specificity of p16/Ki-67 staining (0.35 vs 0.28; P = .002), but this was not true for CIN-2/3 (0.35 vs 0.31; P = .063). For predicting CIN-2/3 and CIN-3, combination testing gave potentially better sensitivity (0.95 and 0.96, respectively) and better specificity (0.49 and 0.50, respectively). CONCLUSIONS: In a population of HPV-positive women, p16/Ki-67 dual staining was more sensitive but less specific than cytology for predicting high-grade CIN. The advantage of using both tests in different combinations is the potential for increasing the specificity or sensitivity in comparison with both methods performed individually. Cancer Cytopathol 2017;125:283-291. © 2016 American Cancer Society.

Papanicolaou smear history in women with low-grade cytology before cervical cancer diagnosis.

BACKGROUND: The purpose of the current study was to examine the screening histories of women diagnosed with invasive cervical cancer (ICC) in 2000 who had previous Papanicolaou (Pap) smears deemed to be unsatisfactory or with low-grade findings that did not lead to biopsy. METHODS: A total of 252 Pap smears from 47 women taken between 1992 and 2000 were included in the study; 247 smears were reexamined at the laboratory of origin before the study and all 252 were then reexamined independently by 2 experienced cytotechnicians and 2 cytopathologists. RESULTS: Of the 47 cases of ICC, 35 were squamous cell carcinoma, 10 were adenocarcinoma, and 2 were other types. On reexamination at the laboratory of origin, 24 cases were upgraded and in the study group 27 cases were upgraded to diagnoses requiring biopsy. On reexamination at the laboratory of origin, it was found that the first high-grade squamous intraepithelial lesion (HSIL) could have been diagnosed on average 4.2 years earlier than it was originally (95% confidence interval [95% CI], 3.3-5.1 years). On reexamination by the study group the first diagnosis of HSIL was made in smears dating from 5.4 years before the diagnosis of ICC (95% CI, 4.5-6.2 years). CONCLUSIONS: The study confirms that unsatisfactory and low-grade Pap smears imply a risk of developing high-grade lesions at a later date and shows that in a screening program a subgroup of smears may be diagnosed as unsatisfactory or low grade despite the presence of high-grade findings that are detectable on reexamination.

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility.

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.