Abstract
Objective
To study patterns of abnormal cervical cancer screening in women aged >60 years and explore the risk and predictors of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).
Methods
This retrospective cohort study examined 1,596 women aged >60 years with abnormal cervical cancer screening results from eight Thai cancer centers. Those who underwent hysterectomy were excluded. Patient characteristics, previous and current cervical cancer screening results, and histopathology data were collected and analyzed.
Results
Mean age was 68.2±7.2 years. The abnormal screening results were normal cytology with positive high-risk human papillomavirus (0.9%), atypical squamous cells of undetermined significance (37.7%), low-grade squamous intraepithelial lesion (12%), atypical squamous cell cannot exclude high-grade lesion (11.7%), high-grade squamous intraepithelial lesion (12.7%), atypical glandular cell (20.1%), squamous cell carcinoma (4.3%), and adenocarcinoma (0.7%). Risk of CIN2+ in women with abnormal screening was 17.9% (95% confidence interval [CI]=16.1–19.8); among those with available histopathology, the risk was 28.8% (95% CI=26.1–31.7). Univariable logistic regression showed that age >70 years, sexual activity within 1 year, previous abnormal/no screening, previous CIN2+ pathology, presence of symptoms, and high-grade cytology were significant predictors of CIN2+. In the multivariable analysis, lack of previous screening (adjusted odds ratio=4.05; 95% CI=1.91–8.60; p<0.001) and high-grade cytology (adjusted odds ratio=7.00; 95% CI=3.34–14.67; p<0.001) were independent predictors of CIN2+.
Conclusion
Continuing cervical cancer screening in women aged >60 years should be individualized based on their risk factors, particularly for those who have never been screened.
Keywords: Cytology, Human Papillomavirus, High-Grade Squamous Intraepithelial Lesion, Aged
Synopsis
Risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were 17.9% in abnormal cervical screened elderly women. Risk of CIN2+ were 28.8% in abnormal cervical elderly women with available pathology. Elderly women who having high-grade cytology or never screening were at increased risk for CIN2+.
INTRODUCTION
Cervical cancer is the second most common cancer in women in Thailand [1]. The age-standardized cervical cancer incidence of 16.4 per 100,000 women in Thailand exceeds the global incidence of 13.3 per 100,000 [2]. This highlights the importance of awareness, screening, and prevention efforts to combat this disease effectively. In 2005, the Thai National Health Security Office and the Ministry of Public Health initiated a national policy for cervical cancer screening which was implemented in three phases. Phase I, from 2005–2009, comprised conventional Pap smear or visual inspection under acetic acid for women aged 35–60 years at 5-year intervals. The program was then extended to phase II (2010–2014) and phase III (2015–2019). Since 2022, human papillomavirus (HPV) testing has been endorsed in the cervical cancer screening process [3,4,5]. This approach has resulted in a substantial decline in the incidence of cervical cancer and cervical cancer-related mortality in Thailand [6].
Although the Thai national guidelines and those in other countries have recommended that cervical cancer screening cease after a certain age [7,8], such screening is still occasionally observed among Thai women who exceed the recommended age range. This extended screening might stem from physicians' concerns about age-specific or individual risks, a lag in adopting updated recommendations, or patients' preferences. Physicians may elect to screen women older than the recommended age for several reasons. First, the incidence of cervical cancer peaks initially in the fifth decade of life and then again after age 60 years [9]. Second, elderly women are more likely to present with advanced stage disease, which has a higher mortality [10]. Third, with a current global trend of longevity, newly acquired HPV infection is certainly possible in older sexually active women [11,12]. Nevertheless, there are no specific guidelines for managing older women with abnormal cervical cancer screening. Therefore, this study aimed to investigate patterns of abnormal cervical cancer screening in women aged >60 years, focusing on risk and predictors of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In this study, CIN2 was selected as the threshold for the study endpoint because, in older individuals, the likelihood of spontaneous regression of CIN2 is generally low, and treatments impacting fertility are not a significant concern [13,14].
MATERIALS AND METHODS
This retrospective cohort study was conducted in eight cancer centers in Bangkok, Thailand. The protocol was approved by the institutional review board of each center as follows: 1) Faculty of Medicine Siriraj Hospital, Mahidol University (COA no. Si400/2021); 2) National Cancer Institute (COA no. 028/2021); 3) Princess Srisavangavadhana College of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy (COA no.036/2564) 4); Faculty of Medicine Vajira Hospital, Navamindradhiraj University (COA no. 183/63); 5) Bhumibol Adulyadej hospital (COA no. 7/64); 6) Phramongkutklao Hospital (COA no. IRBRTA0333/2564); 7) Rajavithi Hospital (COA no.212/2563); and 8) Faculty of Medicine Srinakharinwirot University (SWUEC-289/2564E). Women aged >60 years who had abnormal cervical cancer screening between January 1, 2003 and June 30, 2020 were eligible for inclusion. Those who underwent hysterectomy were excluded.
The following data were collected: demographics, number of pregnancies, human immunodeficiency virus infection status, history of gynecologic disease, tobacco smoking/exposure, HPV vaccination, sexual activity within 1 year, previous and most recent cervical cancer screenings, indication for screening, subsequent testing and treatment, histopathology results, and follow-up clinical data. The primary outcome was intermediate risk of CIN2+. Secondary outcomes were pattern of abnormal cervical cancer screening and predictors of CIN2+ pathology.
Categorical variables are presented as frequencies with percentage. Continuous variables with a normal distribution are presented as means with standard deviation; those with a non-normal distribution are presented as medians with interquartile range (IQR). Risk of CIN2+ was established using simple proportions with 95% confidence intervals (CIs) calculated using Wilson’s method. Predictors of CIN2+ pathology were analyzed using univariable and multivariable logistic regression to estimate odd ratios (ORs) and adjusted ORs (aORs). Variables with p<0.1 in univariate analysis were entered into the multivariate model for further analysis. Complete case analysis was used to approach missing values for any variables. The value of p<0.05 was considered significant. Statistical analyses were performed using PASW Statistics version 18.0 (SPSS, Inc., Chicago, IL, USA).
RESULTS
Among the 1,622 women with abnormal cervical cancer screening during the study period, 26 who underwent hysterectomy were excluded. Therefore, 1,596 women were included for analysis. Among these, corresponding pathology for the initial abnormal cervical cancer screening was available in 990 women; 998 women had corresponding pathology available during follow up. Mean age was 68.2±7.2 years. Patient characteristics are presented in Table 1. Most women were not smokers nor had been exposed to tobacco smoke (95.7%). Prevalence of multiparity was 83.8%. Almost all women were human immunodeficiency virus negative (98.9%) and most reported no sexual activity in the past year (88.9%). Among the 195 women in whom HPV vaccination data was available, 97.4% had never received the vaccine. Slightly over one-third of women never had cervical cancer screening before (36.9%). Most women underwent cervical cancer screening during a routine check-up and reported no relevant symptoms.
Table 1. Patient characteristics.
| Variables | Values | |
|---|---|---|
| Parity (n=1,402) | ||
| 0 | 89 (6.3) | |
| 1 | 138 (9.8) | |
| >1 | 1,175 (83.8) | |
| HIV infection (n=1,310) | ||
| No | 1,295 (98.9) | |
| Yes | 15 (1.1) | |
| Tobacco smoke exposure (n=782) | ||
| No | 748 (95.7) | |
| Yes | 34 (4.3) | |
| HPV vaccination (n=195) | ||
| Yes | 5 (2.6) | |
| No | 190 (97.4) | |
| Sexual activity within 1 yr (n=494) | ||
| No | 439 (88.9) | |
| Yes | 55 (11.1) | |
| Prior cervical cancer screening (n=1,295) | ||
| Yes, normal | 478 (36.9) | |
| Yes, abnormal | 329 (25.4) | |
| Never | 488 (37.7) | |
| Prior CIN2+ lesion (n=1,503) | 106 (7.1) | |
| Clinical presentation (n=1,573) | ||
| Check up | 972 (61.8) | |
| Surveillance of precancerous cervical lesion | 94 (6.0) | |
| Abnormal uterine bleeding | 333 (21.2) | |
| Vaginal discharge | 62 (3.9) | |
| Pelvic pain | 34 (2.1) | |
| Vulvovaginal lesion | 16 (1.0) | |
| Other symptoms* | 62 (3.9) | |
Values are presented as number (%).
CIN2+, cervical intraepithelial neoplasia grade 2 or worse; HIV, human immunodeficiency virus; HPV, human papillomavirus.
*Uterovaginal prolapse, urinary symptoms, pruritus vulvae, and pelvic mass.
The pattern of abnormal cervical cancer screening is shown in Table 2. The prevalence of low-grade cytology and high-grade cytology was similar (50.7% and 49.5%, respectively). The third most common abnormal cytology was atypical squamous cells of undetermined significance (37.7%), followed by atypical glandular cell (20.1%), and high-grade squamous intraepithelial lesion (12.7%). Squamous cell carcinoma and adenocarcinoma were found in 4.3% and 0.7% of patients, respectively. Only 126 women underwent HPV testing. Among these, 4.3% were positive for non 16/18 high-risk HPV and 1.2% were positive for HPV 16/18.
Table 2. Abnormal cervical cancer screening results.
| Cytology | Total (n=1,596) | HPV testing | ||||
|---|---|---|---|---|---|---|
| Yes (n=126) | No (n=1,470) | |||||
| Negative | Positive HR, Non 16/18 | Positive HR, 16/18 | ||||
| Normal/NA | 16 (1.0) | |||||
| NA | 1 (0.1) | 0 (0.0) | 1 (0.1) | 0 (0.0) | 0 (0.0) | |
| Normal | 15 (0.9) | 0 (0.0) | 11 (0.7) | 4 (0.3) | 0 (0.0) | |
| Low grade cytology | 792 (49.7) | |||||
| ASCUS | 601 (37.7) | 21 (1.3) | 22 (1.4) | 3 (0.2) | 555 (34.8) | |
| LSIL | 191 (12.0) | 1 (0.1) | 21 (1.3) | 3 (0.2) | 166 (10.4) | |
| High grade cytology | 709 (44.5) | |||||
| ASC-H | 187 (11.7) | 7 (0.4) | 2 (0.1) | 5 (0.3) | 173 (10.8) | |
| HSIL | 202 (12.7) | 2 (0.1) | 9 (0.6) | 1 (0.1) | 190 (11.9) | |
| AGC | 320 (20.1) | 6 (0.4) | 1 (0.1) | 0 (0.0) | 313 (19.6) | |
| Cancer | 79 (5.0) | |||||
| SCCA | 68 (4.3) | 2 (0.1) | 1 (0.1) | 3 (0.2) | 62 (3.9) | |
| Adenocarcinoma | 11 (0.7) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 11 (0.7) | |
| Total | 1,596 (100.0) | 39 (2.4) | 68 (4.3) | 19 (1.2) | 1,470 (92.1) | |
Values are presented as number (%).
AGC, atypical glandular cell; ASC-H, atypical squamous cell cannot exclude HSIL; ASCUS, atypical squamous cells of undetermined significance; HPV, human papillomavirus; HR, high-risk; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; NA, not available; SCCA, squamous cell carcinoma.
The corresponding pathology for all cervical cancer screening results is shown in Table S1. After excluding women with unavailable histopathology and those diagnosed with other gynecologic cancers (endometrial, ovarian, or vulvar), the analyses of immediate and cumulative risk of CIN2+ are shown in Table 3. Overall immediate risk of CIN2+ was 28.8% (95% CI=26.1–31.7). Median follow-up was 13.9 months (IQR=8.9–20.6). The cumulative risk of CIN2+ during follow-up was 30.7% (95% CI=27.9–33.6). The initial management and subsequent pathology during follow-up are shown in Fig. S1.
Table 3. Immediate and cumulative risk of CIN2+ by screening results.
| Screening results | No. | Immediate risk of CIN2+, % (95% CI) | No. | Cumulative risk of CIN2+, % (95% CI) | |
|---|---|---|---|---|---|
| Normal/no cytology | 1/14 | 7.1 (1.3–31.5) | 3/14 | 21.4 (7.6–47.6) | |
| Positive HR HPV, non16/18 | 1/11 | 9.1 (1.6–37.7) | 1/11 | 7.1 (1.3–31.5) | |
| Positive HR HPV, 16/18 | 0/3 | 0 (0–56.2) | 2/3 | 66.7 (20.8–93.9) | |
| ASCUS | 27/331 | 8.2 (5.7–11.6) | 33/340 | 9.7 (6.9–13.2) | |
| Negative HR HPV | 0/5 | 0 (0–43.5) | 0/5 | 0 (0–43.5) | |
| Positive HR HPV, non16/18 | 3/17 | 17.6 (6.2–41.0) | 4/17 | 23.5 (9.6–47.3) | |
| Positive HR HPV, 16/18 | 0/2 | 0 (0–65.8) | 0/2 | 0 (0–65.8) | |
| No HPV result | 24/307 | 7.8 (5.3–11.4) | 29/316 | 9.2 (6.5–12.9) | |
| LSIL | 6/145 | 4.1 (1.9–8.7) | 10/145 | 6.9 (3.8–12.2) | |
| Negative HR HPV | 0/1 | 0 (0–79.3) | 0/1 | 0 (0–79.3) | |
| Positive HR HPV, non16/18 | 2/19 | 10.5 (2.9–31.4) | 2/19 | 10.5 (2.9–31.4) | |
| No HPV result | 4/125 | 3.2 (1.3–7.9) | 8/125 | 6.4 (3.3–12.1) | |
| ASC-H | 47/143 | 32.9 (25.7–40.9) | 50/143 | 34.9 (27.6–43.1) | |
| Negative HR HPV | 2/4 | 50 (15.0–85.0) | 2/4 | 50 (15.0–85.0) | |
| Positive HR HPV, non16/18 | 0/2 | 0 (0–65.8) | 0/2 | 0 (0–65.8) | |
| Positive HR HPV, 16/18 | 0/3 | 0 (0–56.2) | 0/3 | 0 (0–56.2) | |
| No HPV result | 45/134 | 33.6 (26.1–41.9) | 48/134 | 35.8 (28.2–44.2) | |
| HSIL | 128/180 | 71.1 (64.1–77.2) | 132/180 | 73.3 (66.4–79.3) | |
| Negative HR HPV | 0/2 | 0 (0–65.8) | 0/2 | 0 (0–65.8) | |
| Positive HR HPV, non16/18 | 7/9 | 77.8 (45.3–93.7) | 7/9 | 77.8 (45.3–93.7) | |
| Positive HR HPV, 16/18 | 1/1 | 100 (20.7–100) | 1/1 | 100 (20.7–100) | |
| No HPV result | 120/168 | 71.4 (64.2–77.7) | 124/168 | 73.8 (66.7–79.9) | |
| AGC | 25/120 | 20.8 (14.5–29.0) | 26/119 | 21.9 (15.4–30.1) | |
| Negative HR HPV | 1/5 | 20 (3.6–62.5) | 1/5 | 20 (3.6–62.5) | |
| No HPV result | 24/115 | 20.9 (14.4–29.2) | 25/114 | 21.9 (15.3–30.4) | |
| CA | 51/57 | 89.5 (78.9–95.1) | 52/57 | 91.2 (81.1–96.2) | |
| Positive HR HPV, non16/18 | 1/1 | 100 (20.7–100) | 1/1 | 100 (20.7–100) | |
| Positive HR HPV, 16/18 | 3/3 | 100 (43.9–100) | 3/3 | 100 (43.9–100) | |
| No HPV result | 47/53 | 88.7 (77.4–94.7) | 48/53 | 90.6 (79.8–95.9) | |
| Total | 285/990 | 28.8 (26.1–31.7) | 306/998 | 30.7 (27.9–33.6) | |
AGC, atypical glandular cell; ASC-H, atypical squamous cell cannot exclude HSIL; ASCUS, atypical squamous cells of undetermined significance; CA, carcinoma; CI, confidence interval; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; HPV, human papillomavirus; HR, high-risk; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion.
The predictors of immediate risk of CIN2+ are demonstrated in Table 4. Significant predictors in the univariable analyses were age >70 years, sexual activity within 1 year, previous abnormal/no cervical cancer screening, previous CIN2+ pathology, presence of symptoms, and high-grade cytology. In the multivariable analysis, the significant predictors were lack of previous screening (aOR=4.05; 95% CI=1.91–8.60; p<0.001) and high-grade cytology (aOR=7.00; 95% CI=3.34–14.67; p<0.001). Of note, women with previous CIN2+ pathology had a higher risk of CIN2+ (aOR=2.22; 95% CI=0.76–6.43), but the finding was not significant (p=0.091).
Table 4. Predictors of immediate risk of CIN2+ pathology.
| Factor | No. | OR (95% CI) | p-value | Adjusted OR (95% CI) | p-value | |
|---|---|---|---|---|---|---|
| Age (yr) | 990 | |||||
| >60–65 | 497 | 1 | 1 | |||
| >65–70 | 209 | 1.17 (0.81–1.68) | 0.414 | 0.78 (0.34–1.79) | 0.557 | |
| >70 | 284 | 1.88 (1.37–2.56) | <0.001 | 0.99 (0.50–1.95) | 0.978 | |
| HIV infection | 792 | |||||
| No | 784 | 1 | ||||
| Yes | 8 | 0.79 (0.16–3.96) | 0.777 | |||
| Tobacco smoke exposure | 601 | |||||
| No | 579 | 1 | ||||
| Yes | 22 | 1.08 (0.42–2.82) | 0.871 | |||
| Sexual activity within 1 yr | 313 | |||||
| No | 278 | 1 | 1 | |||
| Yes | 35 | 0.45 (0.20–1.03) | 0.060 | 0.97 (0.37–2.60) | 0.959 | |
| Prior cervical cancer screening | 792 | |||||
| Yes, normal | 306 | 1 | 1 | |||
| Yes, abnormal | 250 | 2.20 (1.45–3.34) | <0.001 | 2.33 (0.82–6.67) | 0.114 | |
| Never | 236 | 5.28 (3.53–7.91) | <0.001 | 4.05 (1.91–8.60) | <0.001 | |
| Prior CIN2+ lesion | 978 | |||||
| No | 897 | 1 | 1 | |||
| Yes | 81 | 2.49 (1.57–3.95) | <0.001 | 2.22 (0.76–6.43) | 0.091 | |
| Clinical presentation | 984 | |||||
| Asymptomatic | 734 | 1 | 1 | |||
| Symptomatic | 250 | 2.67 (1.98–3.62) | <0.001 | 1.40 (0.72–2.71) | 0.316 | |
| Current cytology | 990 | |||||
| Low grade | 490 | 1 | 1 | |||
| High grade | 500 | 13.52 (9.15–19.97) | <0.001 | 7.00 (3.34–14.67) | <0.001 | |
The p-values in bold are statistically significant.
CI, confidence interval; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; HIV, human immunodeficiency virus; OR, odds ratio.
DISCUSSION
This study found that the immediate risk of CIN2+ in women aged >60 years was 17.9% in those with abnormal screening overall and 28.8% in those with abnormal screening whose histopathology was available. These rates are higher than those reported in prior studies. In a study of Danish women aged 69 years and older, CIN2+ was detected in 11% of HPV-positive women and 18% of HPV-positive women whose histology was available [15]. In another study, the immediate risk of CIN2+ in HPV-positive elderly women was 20%, which increased to 24.4% during follow-up [10]. The corresponding immediate and cumulative risks in our patients were higher (28.8% and 30.7%, respectively). Several reasons may explain why our rates were higher. First, most women in our study had cytology-based screening, not just HPV testing. Cytologic testing has higher specificity than HPV testing [10,16]. Second, the prevalence of CIN2+ varies according to geographic location, which might be caused by variations in socioeconomic factors, public health policy, and accessibility to cervical cancer prevention programs. Regarding the cumulative rate of CIN2+ in our study which was slightly increased during follow-up (from 28.8% to 30.7%), this was probably due to short follow up time (median of 13.9 months) comparing to in the study of Booth et al (from 20% to 24.4%) who had a longer period of follow-up (36 months) [10].
The immediate risk of CIN2+ seemed to be lower in our patients, whose ages exceed that of the recommended age range for cervical cancer screening, than in previously reported cohorts, whose ages were within the recommended range (Table 5) [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. This might be explained by age-specific patterns of virulent HPV 16/18 infection and physiologic changes in the cervix after menopause. Previous studies have reported that the HPV 16/18 positivity rate decreases with increasing age [35]. Atrophic changes in the cervical epithelial cells caused by postmenopausal low estrogen levels might not be a suitable environment for supporting the HPV. Furthermore, degenerative cells can be misinterpreted as cervical intraepithelial neoplasia [36,37]. Our findings appear to correlate with those of a previous study which showed that the risk of CIN2+ peaks between ages 35 to 49 years and then decreases with age [28,38].
Table 5. Immediate risk of CIN2+ in Thai women according to cervical cancer screening results and age.
| Screening results | Immediate risk of CIN2+ (%) | ||
|---|---|---|---|
| Age within recommended age range | Age beyond recommended age range (our study) | ||
| Study and year | Risk | Risk | |
| Normal/no cytology with positive HR HPV | Supho et al. (2014) [17] | 2.7 | 7.1 |
| Paengchit et al. (2014) [18] | 11.2 | ||
| ASCUS | Lertvutivivat et al. (2016) [19] | 5.3 | 8.2 |
| Kantathavorn et al. (2008) [31] | 13.9 | ||
| Heng and Sirichaisutdhikorn (2016) [20] | 16.6 | ||
| Poomtavorn et al. (2011) [21] | 23.6 | ||
| Kietpeerakool et al. (2014) [22] | 8.0–18.5 | ||
| LSIL | Jareemit et al. (2022) [23] | 6 | 4.1 |
| Vanichtantikul et al. (2021) [34] | 11.1 | ||
| Kiatiyosnusorn et al. (2010) [24] | 29.8 | ||
| Kietpeerakool et al. (2014) [22] | 11.2–30.3 | ||
| ASC-H | Phaliwong et al. (2018) [25] | 15.3 | 32.9 |
| Lertvutivivat et al. (2016) [19] | 30 | ||
| Atjimakul et al. (2013) [32] | 33.9 | ||
| Kietpeerakool et al. (2014) [22] | 10.5–56.5 | ||
| AGC | Phaliwong et al. (2018) [25] | 11.3 | 20.8 |
| Sawangsang et al. (2011) [26] | 15.8 | ||
| Chatchotikawong et al. (2012) [27] | 24.6 | ||
| HSIL | Boonlikit (2008) [28] | 75.7 | 71.1 |
| Kantathavorn et al. (2021) [33] | 95.5 | ||
| Kietpeerakool et al. (2014) [22] | 62.2–73.7 | ||
| CA | Kingnate et al. (2016) [29] | 93.5 | 89.5 |
| Ruengkhachorn et al. (2012) [30] | 97.7 | ||
AGC, atypical glandular cell; ASC-H, atypical squamous cell cannot exclude HSIL; ASCUS, atypical squamous cells of undetermined significance; CA, carcinoma; CIN2+, cervical intraepithelial neoplasia 2 or worse; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion.
There is currently a lack of evidence to support whether women with abnormal cervical cancer screening results who are older than the recommended age for screening should be managed using the same guidelines as those who are within the recommended age range. According to the 2019 American Society of Colposcopy and Cervical Pathology guidelines, management is based on an estimated immediate risk of cervical intraepithelial neoplasia 3 or worse (CIN3+), which accounts for a combination of previous and present screening results. Immediate colposcopy is recommended if the estimated immediate risk of CIN 3+ exceeds 4% [39]. CIN3 is preferred in the guidelines as a surrogate endpoint rather than CIN2 because CIN3 is a more reproducible diagnosis [39]. Moreover, CIN2 has been associated with high spontaneous regression rates and overtreatment is a concern, especially in women who would like to maintain fertility. However, in older women, the rate of spontaneous regression is generally low and treatment affecting fertility is not a primary concern [39]. CIN2 may therefore be used as the endpoint in older women. More evidence is required for age-specific risk-based management guidelines both in general and in older women.
The older women in our study who had never been screened before and those with high-grade cytology were at significantly greater risk of CIN2+; prior CIN2+ pathology did not significantly increase the risk. Previous studies have demonstrated that prior screening decreases the risk of a cervical cancer diagnosis [40]. Unscreened women may harbor undetected HPV which can cause a precancerous lesion or cancer of the cervix. Our results support the guideline recommendation to extend screening to older women if they have not been screened before and women with a history of CIN2+ [7].
This study has some limitations. First, any retrospective study with incomplete data is subject to bias. Second, a central pathology review was not conducted to ensure diagnostic consistency. Third, only 7.8% of subjects underwent HPV testing. Finally, we enrolled only older women with abnormal cervical cancer screening; we did not include those with normal screening results. As a result, the true prevalence of CIN2+ in older women cannot be evaluated. Nevertheless, this is the first large-scale study from Thailand to examine the immediate risk of CIN2+ among older women with abnormal cervical cancer screening results who were screened, diagnosed, and managed in multiple cancer cancers.
As life expectancy increases in Thailand and around the world, it is essential to conduct studies aimed at improving medical care in older individuals. This study provides data regarding the risk of CIN2+ among older women with abnormal cervical cancer screening, which is influenced by screening history and cytology grade. However, further study is required before implementing changes in screening policy and patient management.
ACKNOWLEDGEMENTS
We thank all the TGCS Research Group Collaborators for data collection and administrative support and Edanz (www.edanz.com/ac) for editing a draft of this manuscript.
Footnotes
Funding: This study was funded by the Siriraj Foundation, Bangkok, Thailand.
Presentation: This study has been presented as the poster presentation at the IGCS 2023 Annual Global Meeting, taking place November 5–7, 2023 in Seoul, Republic of Korea.
Conflict of Interest: No potential conflict of interest relevant to this article was reported.
- Conceptualization: J.N., K.W., T.S., K.R., I.P., K.N.
- Data curation: J.N.
- Formal analysis: J.N.
- Funding acquisition: I.P.
- Investigation: J.N., K.W., T.J., T.S., K.R., I.P., K.N.
- Methodology: J.N., K.W., T.J., T.S., K.R., I.P., K.N.
- Project administration: J.N., T.S., K.N.
- Resources: J.N., K.W., T.S., K.R., I.P., K.N.
- Supervision: T.S., I.P.
- Visualization: J.N., T.S.
- Writing - original draft: J.N., K.W., T.J., K.N.
- Writing - review & editing: J.N., K.W., T.J., T.S., K.R., I.P., K.N.
SUPPLEMENTARY MATERIALS
Pathology according to cervical cancer screening results
Management and subsequent pathology during follow-up stratified by initial cervical cytology. Other gynecologic cancers include endometrial, ovarian, and vulvar.
References
- 1.Wongpratate M, Bumrungthai S. Cervical cancer in Thailand: 2023 update. Obstet Gynecol Sci. 2024;67:261–269. doi: 10.5468/ogs.23277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ferlay JEM, Lam F, Columbet M, Mery L, Pineros M. Global cancer observatory: cancer today. Lyon: International Agency for Research on Cancer; 2020. [Google Scholar]
- 3.Ploysawang P, Rojanamatin J, Prapakorn S, Jamsri P, Pangmuang P, Seeda K, et al. National cervical cancer screening in Thailand. Asian Pac J Cancer Prev. 2021;22:25–30. doi: 10.31557/APJCP.2021.22.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Wilailak S, Lertchaipattanakul N. The epidemiologic status of gynecologic cancer in Thailand. J Gynecol Oncol. 2016;27:e65. doi: 10.3802/jgo.2016.27.e65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kengsakul M, Laowahutanont P, Wilailak S. Experiences in the prevention and screening of cervical cancer within Thailand. Int J Gynaecol Obstet. 2021;152:48–52. doi: 10.1002/ijgo.13481. [DOI] [PubMed] [Google Scholar]
- 6.Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors. Eur J Cancer. 2013;49:3262–3273. doi: 10.1016/j.ejca.2013.04.024. [DOI] [PubMed] [Google Scholar]
- 7.Fontham ETH, Wolf AMD, Church TR, Etzioni R, Flowers CR, Herzig A, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70:321–346. doi: 10.3322/caac.21628. [DOI] [PubMed] [Google Scholar]
- 8.Chittithaworn S, Charakorn C, Kongsawatvorakul C. Cervical cancer screening guidelines: an updated review. Thai J Obstet Gynaecol. 2021;29:186–190. [Google Scholar]
- 9.Hanprasertpong T, Dhanaworavibul K, Leetanaporn K, Hanprasertpong J. Cervical cancer screening in elderly women. Thai J Obstet Gynaecol. 2022;30:370–375. [Google Scholar]
- 10.Booth BB, Tranberg M, Gustafson LW, Christiansen AG, Lapirtis H, Krogh LM, et al. Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test. BMC Cancer. 2023;23:405. doi: 10.1186/s12885-023-10888-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Shen Y, Xia J, Li H, Xu Y, Xu S. Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women. BMC Womens Health. 2021;21:80. doi: 10.1186/s12905-021-01217-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Beckman N, Waern M, Gustafson D, Skoog I. Secular trends in self reported sexual activity and satisfaction in Swedish 70 year olds: cross sectional survey of four populations, 1971–2001. BMJ. 2008;337:a279. doi: 10.1136/bmj.a279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Tainio K, Athanasiou A, Tikkinen KAO, Aaltonen R, Cárdenas J, Hernándes, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018;360:k499. doi: 10.1136/bmj.k499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Bekos C, Schwameis R, Heinze G, Gärner M, Grimm C, Joura E, et al. Influence of age on histologic outcome of cervical intraepithelial neoplasia during observational management: results from large cohort, systematic review, meta-analysis. Sci Rep. 2018;8:6383. doi: 10.1038/s41598-018-24882-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.St-Martin G, Viborg PH, Andersen ABT, Andersen B, Christensen J, Ejersbo D, et al. Histological outcomes in HPV-screened elderly women in Denmark. PLoS One. 2021;16:e0246902. doi: 10.1371/journal.pone.0246902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Phoolcharoen N, Kantathavorn N, Sricharunrat T, Saeloo S, Krongthong W. A population-based study of cervical cytology findings and human papillomavirus infection in a suburban area of Thailand. Gynecol Oncol Rep. 2017;21:73–77. doi: 10.1016/j.gore.2017.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Supho B, Supoken A, Kleebkaew P, Kietpeerakool C. Cervical pathology in high-risk human papillomavirus- positive, cytologically normal women. Asian Pac J Cancer Prev. 2014;15:7977–7980. doi: 10.7314/apjcp.2014.15.18.7977. [DOI] [PubMed] [Google Scholar]
- 18.Paengchit K, Kietpeerakool C, Wangchai W, Pouraeng S, Lalitwongsa S. Cervical pathology in cytology-negative/HPV-positive women: results from Lampang Cancer Hospital, Thailand. Asian Pac J Cancer Prev. 2014;15:7951–7954. doi: 10.7314/apjcp.2014.15.18.7951. [DOI] [PubMed] [Google Scholar]
- 19.Lertvutivivat S, Chanthasenanont A, Chanthasenanont A, Muangto T, Nanthakomon T, Pongrojpaw D, et al. Silent high grade cervical intraepithelial neoplasia in atypical smears from liquid based cervical cytology - three years experience in Thammasat University Hospital. Asian Pac J Cancer Prev. 2016;17:4353–4356. [PubMed] [Google Scholar]
- 20.Heng S, Sirichaisutdhikorn D. Incidence of high-grade squamous intraepithelial lesions in patients with atypical squamous cells of undetermined significance Papanicolaou smears at Naresuan University Hospital. Asian Pac J Cancer Prev. 2016;17:2411–2414. [PubMed] [Google Scholar]
- 21.Poomtavorn Y, Suwannarurk K, Thaweekul Y, Maireang K. Risk factors for high-grade cervical intraepithelial neoplasia in patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou smears. Asian Pac J Cancer Prev. 2011;12:235–238. [PubMed] [Google Scholar]
- 22.Kietpeerakool C, Tangjitgamol S, Srisomboon J. Histopathological outcomes of women with abnormal cervical cytology: a review of literature in Thailand. Asian Pac J Cancer Prev. 2014;15:6489–6494. doi: 10.7314/apjcp.2014.15.16.6489. [DOI] [PubMed] [Google Scholar]
- 23.Jareemit N, Horthongkham N, Therasakvichya S, Viriyapak B, Inthasorn P, Benjapibal M, et al. Human papillomavirus genotype distribution in low-grade squamous intraepithelial lesion cytology, and its immediate risk for high-grade cervical lesion or cancer: a single-center, cross-sectional study. Obstet Gynecol Sci. 2022;65:335–345. doi: 10.5468/ogs.22025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kiatiyosnusorn R, Suprasert P, Srisomboon J, Siriaree S, Khunamornpong S, Kietpeerakool C. High-grade histologic lesions in women with low-grade squamous intraepithelial lesion cytology from a region of Thailand with a high incidence of cervical cancer. Int J Gynecol Obstet. 2010;110:133–136. doi: 10.1016/j.ijgo.2010.03.022. [DOI] [PubMed] [Google Scholar]
- 25.Phaliwong P, Pariyawateekul P, Khuakoonratt N, Sirichai W, Bhamarapravatana K, Suwannarurk K. Cervical cancer detection between conventional and liquid-based cervical cytology: a 6-year experience in northern Bangkok Thailand. Asian Pac J Cancer Prev. 2018;19:1331–1336. doi: 10.22034/APJCP.2018.19.5.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Sawangsang P, Sae-Teng C, Suprasert P, Srisomboon J, Khunamornpong S, Kietpeerakool C. Clinical significance of atypical glandular cells on Pap smears: experience from a region with a high incidence of cervical cancer. J Obstet Gynaecol Res. 2011;37:496–500. doi: 10.1111/j.1447-0756.2010.01387.x. [DOI] [PubMed] [Google Scholar]
- 27.Chatchotikawong U, Ruengkhachorn I, Laiwejpithaya S. Factors predicting pathologic significance among women with atypical glandular cells on liquid-based cytology. Int J Gynaecol Obstet. 2012;119:30–34. doi: 10.1016/j.ijgo.2012.05.027. [DOI] [PubMed] [Google Scholar]
- 28.Boonlikit S. Prevalence of high-grade cervical lesion in women with LSIL and HSIL cytology and prevalence of invasive cancer in women cytologically positive for malignancy. Asian Pac J Cancer Prev. 2008;9:715–718. [PubMed] [Google Scholar]
- 29.Kingnate C, Tangjitgamol S, Khunnarong J, Manusirivithaya S. Abnormal uterine cervical cytology in a large tertiary hospital in Bangkok metropolis: prevalence, management, and outcomes. Indian J Cancer. 2016;53:67–73. doi: 10.4103/0019-509X.180827. [DOI] [PubMed] [Google Scholar]
- 30.Ruengkhachorn I, Laiwejpithaya S, Leelaphatanadit C, Chaopotong P. Clinicopathologic importance of women with squamous cell carcinoma cytology on Siriraj liquid-based cervical cytology. Asian Pac J Cancer Prev. 2012;13:4567–4570. doi: 10.7314/apjcp.2012.13.9.4567. [DOI] [PubMed] [Google Scholar]
- 31.Kantathavorn N, Kietpeerakool C, Suprasert P, Srisomboon J, Khunamornpong S, Nimmanhaeminda K, et al. Clinical relevance of atypical squamous cells of undetermined significance by the 2001 Bethesda system: experience from a cervical cancer high incidence region. Asian Pac J Cancer Prev. 2008;9:785–788. [PubMed] [Google Scholar]
- 32.Atjimakul T, Boonyapipat S, Chichareon S, Phukaoloun M. Cytomorphologic and clinical factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) smears. J Med Assoc Thai. 2013;96:1389–1394. [PubMed] [Google Scholar]
- 33.Kantathavorn N, Yuan V, Vanichtantikul A, Krisorakun W, Wetcho T, Ittiamornlert P, et al. Prevalence of high-grade cervical lesion (CIN 2+) in Thai women with high-grade squamous intraepithelial lesion cytology. J Med Assoc Thai. 2021;104(Suppl 2):S34–S39. [Google Scholar]
- 34.Vanichtantikul A, Kantathavorn N, Pena A, Krisorakun W, Wetcho T, Sricharunrat T, et al. Prevalence of high-grade cervical lesion (CIN 2+) in women with low-grade squamous intraepithelial lesion cytology. J Med Assoc Thai. 2021;104(Suppl 2):S15–S19. [Google Scholar]
- 35.Aro K, Nieminen P, Louvanto K, Jakobsson M, Virtanen S, Lehtinen M, et al. Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women. Gynecol Oncol. 2019;154:354–359. doi: 10.1016/j.ygyno.2019.05.024. [DOI] [PubMed] [Google Scholar]
- 36.Dresang LT. Colposcopy: an evidence-based update. J Am Board Fam Pract. 2005;18:383–392. doi: 10.3122/jabfm.18.5.383. [DOI] [PubMed] [Google Scholar]
- 37.Castle PE, Bulten J, Confortini M, Klinkhamer P, Pellegrini A, Siebers AG, et al. Age-specific patterns of unsatisfactory results for conventional Pap smears and liquid-based cytology: data from two randomised clinical trials. BJOG. 2010;117:1067–1073. doi: 10.1111/j.1471-0528.2010.02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.McClung NM, Gargano JW, Park IU, Whitney E, Abdullah N, Ehlers S, et al. Estimated number of cases of high-grade cervical lesions diagnosed among women - United States, 2008 and 2016. MMWR Morb Mortal Wkly Rep. 2019;68:337–343. doi: 10.15585/mmwr.mm6815a1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2020;24:102–131. doi: 10.1097/LGT.0000000000000525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Wang J, Andrae B, Sundström K, Ploner A, Ström P, Elfström KM, et al. Effectiveness of cervical screening after age 60 years according to screening history: Nationwide cohort study in Sweden. PLoS Med. 2017;14:e1002414. doi: 10.1371/journal.pmed.1002414. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Pathology according to cervical cancer screening results
Management and subsequent pathology during follow-up stratified by initial cervical cytology. Other gynecologic cancers include endometrial, ovarian, and vulvar.