1. Introduction

Cervical intraepithelial neoplasia (CIN) represents the preinvasive disease of the uterine cervix. Progression from a CIN to invasive cervical cancer is typically slow, offering a valuable window for intervention. Prevention programs that combine high-risk human papillomavirus (HR-HPV) DNA testing with cervical cytology provides early detection of the cervical abnormalities and help minimize missed diagnoses [1, 2, 3, 4, 5].

In March 2020, the World Health Organization declared COVID-19 a pandemic, profoundly altering healthcare delivery worldwide. During a pandemic, to preserve critical resources, each country introduced various system-wide modifications [6]. As a result, most surgical procedures were deferred, with many cancer patients experiencing significant delays. Professional societies stratified interventions by urgency and recommended postponement of all elective procedures. Likewise, screening programs and colposcopic evaluation of preinvasive cervical and vulvar lesions were incorporated into this triage framework.

The Society of Gynecologic Oncology (SGO) classified vulvar intraepithelial neoplasia (VIN II–III), vaginal intraepithelial neoplasia (VAIN II–III) and high-grade cervical intraepithelial neoplasia (CIN II–III) as non-urgent, permitting delays of up to 12 weeks. The American Society for Colposcopy and Cervical pathology (ASCCP) guidelines similarly allowed follow-up for high-grade cervical screening abnormalities to be deferred for up to three months, and for low-grade abnormalities for 6–12 months. Furthermore, individuals with high-grade cervical disease without suspicion of invasion were advised to schedule evaluation within three months, while those with suspected invasive disease required assessment within four weeks of the initial report [7, 8].

The first case of the novel coronavirus was reported in March 2020 in Turkey. Following a circular issued that month by the Turkish Ministry of Health, all elective surgeries were suspended, and both the national screening program and colposcopic evaluation of preinvasive cervical and vulvar lesions were postponed. In this study, we reported our center’s experience with delayed colposcopies and explore potential causes of these delays. We also examine the relationship between oral contraceptive use and tobacco use with the HPV status and colposcopic biopsy outcomes. To our knowledge, this is the first study to evaluate colposcopy delays during the COVID-19 pandemic, and it may serve as a guide for managing similar latency in future public health crises.

2. Materials and methods

Our colposcopy unit is one of three referral centers for Turkey’s national HPV cancer screening program, which is coordinated by the Early Diagnosis, Screening and Training of Cancer Centers (KETEM). This program relies on primary high-risk HPV (HR-HPV) testing, with colposcopy ordinarily scheduled 15–30 days after referral. However, at the onset of the COVID-19 pandemic, all scheduled colposcopies were cancelled.

Patients whose appointments were postponed received detailed explanations of the delay; once the “new normal” protocols were in place, the unit reopened in June 2020 and patients were rescheduled. Between March and June 2020, 220 women had been booked for colposcopy; 158 ultimately attended follow-up, while the remainder were lost to follow-up. This retrospective cohort study was approved by Etlik Zübeyde Hanim Women’s Health, Training and Research Hospital Training Plan and Coordination Board Committee (05/2020-No: 7). Ethics approval and consent to participate were obtained.

In this retrospective study, we recruited 158 patients and analysed the following information; age of diagnosis, smoking status, age at first coitus, oral contraceptive use, number of sexual partner, menopausal status, colposcopy delayed duration (from the date of the HPV-cytology result to the colposcopy date), cytology, HPV status, colposcopic findings and pathologic results based on the patients’ charts and medical files. While we included all cases that refer to the colposcopy unit; patients who had refuse to apply excluded. We could not obtain any information about these lost cases.

All colposcopies were performed by gynecologic oncologists using a Leica CLS 150 XC MS5 colposcope (Wetzlar, HE, Germany). After applying 3% acetic acid to the cervix, lesions were described according to color, borders, and vascular patterns. Punch biopsy procedure performed in the cases that have abnormal colposcopic findings such as acetowhite area, mosaic pattern, punctuation, rag sign, ulceration and inadequate colposcopic procedure. Histopathologic diagnoses were categorized as: negative for intraepithelial lesion or malignancy (NILM), low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), and squamous intraepithelial lesion (SIL).

Statistical data analysis was performed using the Statistical Package for the Social Sciences version 21 (SPSS Inc, Chicago, IL, USA). Continuous variables were assessed for normality using histograms, the Kolmogorov-Smirnov test, and the Shapiro-Wilk test. The categorical data were analyzed using descriptive statistical methods and correlations between length of duration and clinicopathological variables were compared by chi-square and Fisher’s exact tests. For continuous data, comparisons utilized Student’s t-test, Mann-Whitney U test, or Kruskal-Wallis test as appropriate. All statistical tests were two-sided, and p-values less than 0.05 were considered statistically significant.

3. Results

The demographic, behavioral, and clinical characteristics of the 158 women are presented in Table 1. The mean age was 42.3 ± 8.7 years (range, 22–64 years), and the mean age at first coitus was 19.6 ± 3.7 years (range, 13–35 years). Correlation of oral contraceptive use, smoking status, age, and HPV status with the colposcopic biopsy results were mentioned in Table 2. A significant relationship was observed between smoking status and biopsy result (p = 0.034), as well as between HPV status and biopsy result (p = 0.032). There were only two patients with cervical cancer who have the initial cytolgy of atypical squamous cells-cannot exclude HSIL (ASC-H) and latency of colposcopic evaulation were under 3 months.

The mean interval between receipt of the HPV-cytology report and performance of colposcopy was 140 days (range, 21–340 days). Patients were stratified into three delay categories: ≤3 months, 3–6 months, and >6 months. Correlations between delay interval and HPV status, highest colposcopic lesion, and histopathological outcome are summarized in Table 3. There were no significant associations between delay duration and histopathological grade (p = 0.642), HPV status (p = 0.126), or severity of the highest colposcopic lesion (p = 0.930).

4. Discussion

The COVID-19 pandemic has profoundly altered global healthcare dynamics, and its impact is evident in gynecologic practice. In response, guidelines and national health policies introduced modified algorithms that became entrenched in clinical workflows. Although several publications have addressed colposcopic management of abnormal cervical screening results during the pandemic, literature remains limited [1, 9, 10, 11, 12].

The joint recommendations of the European Federation for Colposcopy (EFC) and the European Society of Gynecological Oncology (ESGO) stratify urgency based on cytologic and histologic findings. Patients with squamous cell carcinoma (SCC), atypical glandular cells-favor neoplastic (AGC-FN), endocervical adenocarcinoma in situ, or adenocarcinoma required evaluation within four weeks of their results. Those with high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells-cannot exclude HSIL (ASC-H), or atypical glandular cells not otherwise specified (AGC-NOS) should undergo assessment within one to three months. Conversely, individuals with a positive high-risk HPV test and normal cytology, a positive high-risk HPV test with atypical squamous cells of undetermined significance (ASCUS), or low-grade squamous intraepithelial lesion (LSIL) may safely defer evaluation for up to six to twelve months, provided they remain asymptomatic [9]. Given these guidelines, we investigated the extent of diagnostic delays induced by the pandemic and their potential associations with clinical and histopathological outcomes.

Appropriate follow-up intervals are critical to reduce the progression of the preinvasive lesions. Clinicians must clearly communicate recommended surveillance schedules while managing patient anxiety. The challenge is to avoid both overtreatment and undertreatment. In our cohort, delays of ≤3 months, 3–6 months, and >6 months were not significantly associated with differences in histopathological outcomes on colposcopic biopsy.

Personalized risk-based management of cervical disease has gained traction under the ASCCP 2019 Guidelines [7]. These guidelines aim to reduce reliance on colposcopy a costly and subjective procedure by leveraging both the declining prevalence of HSIL in vaccinated populations and individualized risk stratification to guide direct referral [10].

In this research, the significant relation between smoking status and colposcopic biopsy results supports the strong influence of smoking on HPV persistence and progression. According to the results of a cohort study that includes 1976 women, smoking increases the risk of HPV by reducing immunity. It increases susceptibility to high-risk HPV infection particularly HPV 16, by lowering specific antibody titers, whereas past smoking exposure exerts no comparable cumulative effect [13]. In a Chinese study the association between smoking behaviors during follow-up and clearance of HPV infection in women with HPV-positive and pathologically normal uterine cervix, investigated using a propensity score matching analysis.

The main finding of the study was that smoking is associated with a decreased clearance of HPV [14].

In our cohort, HPV genotype was significantly associated with lesion grade, whereas no correlation emerged between delay duration and HPV status. A prospective Chinese study demonstrated that HSILs associated with HPV 16 were the largest, followed by those related to HPV 31/33 and HPV 18 [15]. Consistent with these findings, we observed that HSILs driven by HPV 16/18 were more prevalent and pronounced than lesions attributed to other high-risk genotypes.

In the present study, neither age at first intercourse nor oral contraceptive use was associated with colposcopic biopsy outcomes, likely reflecting our limited sample size. However, previous research has linked early onset of sexual activity to increased risk of disease progression among HPV-positive women [16, 17]. While active HPV infection often reflects recent exposure, latent or persistent infections may be influenced by past sexual behavior [18]. Conversely, oral contraceptive use has been identified as a key risk factor for cervical neoplasia and potentially accelerating epithelial maturation and lesion development [19, 20].

5. Conclusions

Cervical cancer preventive strategies continue to evolve, with variations in implementation and timing across different real-world settings. The COVID-19 pandemic disrupted healthcare systems all around the world. It had changed the timelines for diagnosis, treatment, and disease. These circumstances highlighted the need for structured management approaches for cervical preinvasive lesions [21, 22]. Although the sample is old and that is the limitation of this study, our findings highlighted the significant role of smoking and HPV genotype in the development of high-grade lesions. Importantly, delays of up to six months did not appear to influence progression to high-grade disease, suggesting that such latency may be acceptable in follow-up protocols.

Abbreviations

HR-HPV, High risk Human Papillomavirus; VIN, vulvar intraepithelial neoplasia; VAIN, vaginal intraepithelial neoplasia; CIN, cervical intraepithelial neoplasia; SCC, squamous cell carcinoma; ASCUS, atypical squamous cells of undetermined significance; LSIL, low grade squamous intraepithelial lesion; HSIL, high grade squamous intraepithelial lesion; AGC-NOS, atypical glandular cells not otherwise specified; AGC-FN, atypical glandular cells, favor neoplastic; ASCCP, American Society for Colposcopy and Cervical pathology; EFC, European Federation for Colposcopy; ESGO, European Society of Gynecological Oncology; SGO, Society of Gynecologic Oncology; KETEM, Early Diagnosis, Screening and Training of Cancer Centers; NILM, negative for intraepithelial lesion or malignancy; SIL, squamous intraepithelial lesion; ASC-H, atypical squamous cells-cannot exclude HSIL.

Availability of data and materials

The data presented in this study are available on reasonable request from the corresponding author.

Author contributions

EIB, FK—Concept/design. EIB, YD, ASDC—Data collection and processing. YD—Analysis and interpretation. EIB—Writing manuscript. NB, EIB—Critical review.

Ethics approval and consent to participate

The study was approved by the Institutional Review Board of Etlik Zübeyde Hanim Women’s Health, Training and Research Hospital (2020-07). As a retrospective study, the requirement for informed consent was waived by the IRB.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.