High‐grade cervical abnormalities and cervical cancer in women following a negative Pap smear with and without an endocervical component: A cohort study with 10 years of follow‐up

Abstract

The proportion of Pap smears containing an endocervical component (ECC) has been declining in Australia. Given that ECC negative (ECC2) smears may be associated with reduced sensitivity, we undertook a retrospective cohort study to estimate rates of histologically confirmed high-grade cervical abnormality (HGA) and cancer in women with negative Pap smears with and without an ECC. Women 18-69 years with at least two Pap smears between 1 January 2001 and 31 December 2010 with the first smear in that period (index smear) showing no abnormality were eligible. Follow-up ended at date of the first abnormal smear, date of histological diagnosis, date of hysterectomy, date of death, or 31 December 2010, whichever came first. ECC status was treated as a time varying exposure. Follow-up was split at each smear after the index smear. Poisson regression was used to estimate adjusted incidence rates and incidence rate ratios (IRR) by ECC status. The incidence rate of histologically confirmed HGA was significantly lower following ECC2 smears than after ECC1 smears (adjusted IRR: 0.69, 95%Confidence Interval (CI) 0.62-0.77), particularly at older ages (interaction between ECC status and age, p 5 0.001). In contrast, the overall rate of invasive cancer was not significantly different after ECC2 than after ECC1 smears (IRR: 1.27, 95%CI 0.90-1.77). In conclusion, women had a lower rate of confirmed HGA and no significant increase in the rate of invasive cervical cancer following ECC2 smears. This study does not support differential (accelerated) follow-up in women with a negative smear without an endocervical component.Substantial reductions in cervical cancer incidence and mortality have been achieved in most developed countries, including Australia, through organized screening programs based on Papanicolaou (Pap) smears. 1 The objective of taking a Pap smear is to sample the transformation zone (TZ) and detect precancerous lesions, if present, and treat them before they develop into cancer. The TZ is the area of the cervix where the transformation from the columnar epithelium to squamous epithelium takes place and is the site where most cervical cancers and intraepithelial lesions develop.1 The presence of columnar cells (also known as endocervical cells or an endocervical component (ECC)) in the smear, although not required for a smear to be "satisfactory for evaluation," is an indication that the TZ has been sampled 2 and traditionally considered an indicator of specimen adequacy. 3Most cross-sectional studies show that the prevalence of cervical intraepithelial neoplasia (CIN) is lower in smears without an ECC (ECC-) than in smears that have an ECC (ECC1). [4][5][6][7] Case-control studies of smears that preceded a histologic diagnosis of CIN and that correctly predicted CIN were more likely to include the ECC than smears that failed to predict the CIN lesion, suggesting that false-negative results may be an issue. 8,9 These findings have raised concerns as to whether Pap smears without ECC are less sensitive in detecting pr...

Worldwide incidence of cervical lesions: a systematic review

“…Six were population-based studies [75][76][77][78][79]83], and three were screening-based studies [80][81][82]. Total follow-up time ranged from 36 months [79] to 216 months [82].…”

“…We further identified nine eligible studies published between 30 September 2012 and 28 February 2014 [75–83], of which four were from Europe [75–78], four from the USA [79–82], and one from Australia [83]. Six were population-based studies [75–79, 83], and three were screening-based studies [80–82]. Total follow-up time ranged from 36 months [79] to 216 months [82].…”

Self‐collected Pap smears may provide an acceptable and effective method of cervical cancer screening

“…26 Indeed, at least 1 study 37 has shown no statistical significance in detection of highgrade abnormalities in patient samples containing an endocervical in comparison with those that do not. More recent research [26][27][28][29][30][31][32]38,39 has shown that the absence of endocervical cells is not necessarily associated with a higher risk of cervical abnormality.…”

ACOG Publications

“…A review of the literature from 2012 to 2019 on whether the absence of a transformation zone component (TZ/EC, i.e., endocervical cells or squamous metaplastic cells) on NILM cytology slides affected patients' subsequent risks of histologic HSIL (CIN 2, CIN 3) diagnoses showed no evidence to change the 2012 recommendations. 83,84…”