Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme

Abstract

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.

False Negative Results in Cervical Cancer Screening—Risks, Reasons and Implications for Clinical Practice and Public Health

“…Adenocarcinoma (ADC), a histological subtype of CC, was identified significantly more frequently than squamous cell carcinoma (SCC) among women with FN cytological results, compared to those with screen-detected cancer, due to their common location in the endocervical canal and more difficult sampling [ 57 , 59 , 60 , 61 ]. Based on the audit of over four thousand CC cases diagnosed in Sweden in 2002–2011, Wang et al concluded that women with normal screening results had an 89% lower risk of SCC and only 60% lower risk of ADC diagnosis [ 62 ].…”

“…Based on the audit of over four thousand CC cases diagnosed in Sweden in 2002–2011, Wang et al concluded that women with normal screening results had an 89% lower risk of SCC and only 60% lower risk of ADC diagnosis [ 62 ]. The risk of obtaining a FN result, compared to a true positive cytology report, was shown to be over three times higher in women subsequently diagnosed with ADC, compared to SCC, and almost two times higher in those with diagnosis of carcinoma other than squamous and glandular type [ 61 ]. It also coincides with the trend of the raising rate of ADCs detection in countries with CC screening implemented; since this type of carcinoma is more difficult to diagnose in screening, the treatment of precancerous lesions is suspended, and they may develop to the fully invasive form of disease [ 63 ].…”

“…Overall, the lower sensitivity of cytological screening for the detection of ADC than SCC is a complex issue and may result from a true lack of abnormal glandular cells on the slide due to: (1) the location of the lesions and less efficient sampling [ 64 ], (2) difficulties in the proper identification of these cells on the slide and abnormal features [ 65 , 66 ], and (3) the possibly faster development and higher rate of progression of ADC precursors [ 67 ]. Data on the performance of cervical cytology in screening for cases of histology, other than SCC and ADC, are scarce [ 61 , 68 , 69 ].…”

Cervical Cancer Prevention in the Era of the COVID-19 Pandemic

“…Individual countries around the world have used the methods listed above (CC screening, HPV vaccination) to create national prevention programs. In Poland, an organized screening program for CC was established in 2006, which involves performing Pap smearbased cervical cytology on women aged 25-59 years at 3-year intervals [17]. In December 2021, The Polish Society of Gynecologist and Obstetricians published recommendations including liquid-based cytology (LBC) in the regimen for cervical cancer (CC) screening.…”

“…The principles of CC prevention in public health care in Poland are presented in Table 1 [5,17,18,22,24], and information regarding the private health care based on the example of the provider included in our study are presented in Table 2 [32].…”