The meaning of high‐risk HPV other than type 16/18 in women with negative cytology: Is it really safe to wait for 1 year?

Abstract

Background Human papillomavirus (HPV) is a primary risk factor for cervical cancer. HPV 16 and 18 are the two most carcinogenic genotypes and have been reported in the majority of cervical cancer. High‐risk HPVs (hrHPVs) other than HPV 16/18 cause approximately a quarter of cervical cancers. We aimed to present the colposcopy‐guided biopsy results of non‐16/18 hrHPV‐infected women with negative cytology. Methods This is a retrospective cohort study conducted on 752 patients between the ages of 30‐65 years with non‐16/18 hrHPV and negative cytology undergoing colposcopy‐guided biopsy at a tertiary gynecological cancer center between January‐2016 and January‐2019. Results The mean age of the women was 42.35±9.41 years. Cervical intraepithelial neoplasia (CIN) 2+ lesion was detected in 49 (6.5%) women with negative cytology. The rate of CIN 2+ lesions in women with abnormal cytology was 12.8%. Patients with abnormal cytology had about 2.1 and 2.4 times increased the odds of CIN 2+ lesion in cervical biopsy and endocervical curettage specimens, respectively. CIN 3+ lesion was detected in 20 (2.7%) women with negative cytology. One (0.1%) of the patients with HPV 39 and negative cytology had invasive cervical cancer. The two most common HPV subtypes were HPV 31 and HPV 51. Conclusions The risk of cervical preinvasive lesions still can be detected and cannot be completely eliminated among hrHPV other than 16/18‐infected women with negative cytology. Based on the results of this study, referral of non‐16/18 hrHPV‐infected women with negative cytology to colposcopy is supported as a credible and feasible strategy.

Prevalence of higher-grade dysplasia in persistently high-risk human papillomavirus positive, cytology negative women after introduction of the new cervical cancer screening in Germany

“…Even though we did not detect any cases of invasive cervical carcinoma, other groups found invasive cervical carcinoma in up to 0.5% of the women [43,44,46]. Interestingly, Giray et al observed that the rate of invasive cancer did not differ significantly between women with normal and abnormal cytology in HPV 16/18 positive women (0.5% vs. 1.5%, p = 0.082) and concluded that Pap testing could be unnecessary in HPV 16/18 positive women who will undergo colposcopy-guided biopsy to diagnose invasive cervical cancer [44].…”

“…While we observed only very few CIN 1 cases (three in total, all of them other hrHPV positive), prevalence of CIN 1 is reported as high as 21.6% in HPV 16/18 positive women [ 44 ] and 23.9% for other hrHPV positive, cytology negative women [ 43 ]. The comparably low number of CIN 1 cases in our study might at least be partially explained by referral for colposcopy only in case of a persistently positive HPV test after 12 months.…”

“…According to their study protocol, ECC specimens and cervical biopsy were mandatorily obtained from all included patients. However, the authors did not provide information on the proportion of the abnormalities which were found by ECC alone and of those where ECC and cervical biopsy yielded the same result (representing cases in which ECC did not provide an extra benefit) [ 43 ].…”

“…In our study, prevalence of CIN 3 was 14% for HPV 16/18 positive women who underwent biopsy and 9% for other hrHPV positive. Reviewing literature, CIN 3 prevalence for the former subgroup ranges from 9.1 to 11.8% [ 44 , 46 , 51 ] and from 2.7 to 14.6% for the latter [ 43 , 46 , 51 ]. However, comparability of the studies among each other and with ours is very limited due to various reasons such as differences in study design (retrospective or prospective), timing of colposcopy (immediate or only in case of repeatedly positive HPV testing at 12 months), threshold for obtaining histological specimens (omission of biopsy in case of normal colposcopic finding or taking a biopsy and/or ECC regardless of colposcopic finding), considered set of patients (all hrHPV positive patients or only those from whom a biopsy was obtained), median age of the study population, method applied for HPV testing and regional prevalence of particular hrHPV types.…”

“…Peace et al reported a CIN 3 + prevalence of 14.7% among HPV 16 positive cases, yet only of 1.4% among HPV 18 positives [ 46 ]. Including only other hrHPV positive cases, Kabaca et al observed a CIN 3 + prevalence of 8.3% for HPV 33 positives, 7.8% for HPV 31 positives and 5.1% for HPV 39 positives [ 43 ]. Compared to Kabaca et al, the CIN 3 prevalence for distinct hrHPV strains in our study collective was a lot higher (HPV 33: 33%, HPV 31: 27%, HPV 52: 33%).…”