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Factors associated with cervical cancer among women in northeastern Iran: a population-based case–control study

This population-based case–control study in northeastern Iran identified increasing age and earlier age at first pregnancy as independent risk factors for cervical cancer, providing evidence to inform targeted prevention strategies despite the modest predictive performance of the developed model.

Original authors: Fatemeh Khabbaz, Ehsanmousa Farkhani, Veda Vakili

Published 2026-08-03

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Fatemeh Khabbaz, Ehsanmousa Farkhani, Veda Vakili

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine the human body as a bustling city, and the immune system as its tireless police force. Usually, this force is excellent at spotting and arresting troublemakers, like viruses that try to sneak in. One such troublemaker is the Human Papillomavirus, or HPV. In most cases, the police catch it quickly, and the virus leaves town without causing any damage. However, sometimes the virus manages to hide and stay in the city for a long time. If it stays too long, it can start to corrupt the local construction plans, turning healthy cells into a chaotic mess called cancer. This is how cervical cancer starts. While scientists know the virus is the main culprit, they are still trying to figure out what other factors might help the virus stay hidden or make the city more vulnerable. Is it the weather (age)? The number of construction projects (pregnancies)? Or maybe the lifestyle of the residents (smoking or diet)? Understanding these clues is crucial because, while we have vaccines and screenings to stop the virus, knowing who is most at risk helps us protect them better.

Now, let's zoom in on a specific neighborhood in northeastern Iran, where a team of researchers decided to play detective. They wanted to solve a mystery: among the women living there, what specific habits or life events were linked to the development of cervical cancer? To do this, they didn't just guess; they set up a massive comparison game. They gathered two groups of women: 74 "cases" who had been diagnosed with cervical cancer (confirmed by a lab test, the gold standard of proof) and 148 "controls" who were healthy and living in the same area. Think of the controls as the "control group" in a science fair experiment—they represent the normal population, allowing the researchers to see what makes the "cases" different.

The researchers looked at a long list of potential suspects: How old were they? How many children did they have? Did they smoke? Were they overweight? Did they have high blood pressure? They used a sophisticated statistical tool called "logistic regression" to weigh the evidence. It's like putting all these clues on a giant scale to see which ones actually tip the balance toward cancer, while ignoring the ones that just look suspicious but aren't actually guilty.

Here is what the investigation revealed. The study found two clear "smoking guns" that were independently linked to the disease. First, age mattered. As women got older, their chances of having cervical cancer went up. Specifically, for every single year a woman aged, her odds of having the disease increased by a tiny but measurable amount (an adjusted odds ratio of 1.043). Second, the age at first pregnancy was a major clue. Women who had their first baby at a younger age had a higher risk. In fact, for every year they waited to have their first child, their risk actually went down (an adjusted odds ratio of 0.918). So, having a baby earlier in life was associated with a higher likelihood of the disease in this group.

However, the study also had some very important "not guilty" verdicts. Many people suspect that things like being overweight (Body Mass Index), having many children (parity), smoking, or having high blood pressure might be the cause. But in this specific study, after doing the math and adjusting for other factors, none of these were found to be independent causes. The data showed no clear link between cervical cancer and BMI, the total number of pregnancies, the age a girl started her period, smoking, or hypertension. The researchers were quite sure about this because they ran the numbers through a rigorous "stress test" called internal validation, which confirmed their model was stable and not just a fluke.

The researchers also checked how good their "detective model" was at predicting who might get sick. They gave it a score called the "Area Under the Curve" (AUC), which is like a grade for a test. The model got a score of 0.666. This isn't a failing grade, but it's not a perfect score either; it suggests the model is okay at telling the difference between sick and healthy women, but it's far from perfect. It means there are still many missing pieces of the puzzle—like the specific status of HPV infection or detailed screening history—that the researchers couldn't include because that data wasn't available in the records they used.

In the end, this study tells us that in northeastern Iran, getting older and having a first pregnancy at a younger age are the two factors most clearly linked to cervical cancer. While the study didn't find proof that smoking or weight were the direct causes in this group, it didn't rule them out as helpers in the bigger picture; it just showed they weren't the main drivers in this specific dataset. The researchers suggest that while their model is a good start, we need more future studies that include more details, like HPV status and social factors, to build a truly complete picture of how to stop this disease. For now, the evidence points to age and early pregnancy as the key players to watch in this part of the world.

Technical Summary: Factors Associated with Cervical Cancer in Northeastern Iran

Problem Statement
Cervical cancer remains a significant global public health challenge, particularly in low- and middle-income countries where nearly 90% of deaths occur. While persistent infection with high-risk human papillomavirus (HPV) is the necessary cause, the progression to invasive cancer is influenced by a complex interplay of demographic, reproductive, behavioral, and socioeconomic factors. In Iran, existing evidence regarding risk factors is limited by a reliance on hospital-based studies, small sample sizes, and restricted geographic scopes, which hinder generalizability. There is a specific lack of robust, population-based evidence from northeastern Iran to inform targeted prevention strategies and risk assessment models.

Methodology
This study employed a population-based retrospective case–control design conducted among women residing in Mashhad and surrounding areas covered by Mashhad University of Medical Sciences (MUMS) between March 21, 2017, and March 19, 2021.

Participants: The study included 222 women: 74 cases with histopathologically confirmed primary cervical cancer identified from the regional Population-Based Cancer Registry, and 148 controls randomly selected from the Primary Health Care (PHC) Family Physician Information System. Controls were selected at a 2:1 ratio to cases to ensure statistical efficiency and comparability.
Data Collection: Demographic, reproductive, lifestyle, and clinical variables were extracted from standardized registry and PHC records. Evaluated factors included age, body mass index (BMI), parity, age at menarche, age at first pregnancy, age at last pregnancy, age at first sexual intercourse, smoking status, hypertension, diabetes, oral contraceptive use, abortion history, and marital status.
Statistical Analysis: Univariable and multivariable logistic regression analyses were performed to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Variables with a univariable $P < 0.20$ or clinical relevance were entered into the multivariable model. Model performance was assessed using the Area Under the Receiver Operating Characteristic Curve (AUC), Hosmer–Lemeshow goodness-of-fit test, Brier score, and Nagelkerke $R^2$ . Internal validation was conducted using 100 iterations of bootstrap resampling to evaluate model stability.

Key Results

Demographic and Clinical Associations: After adjusting for potential confounders, increasing age was independently associated with higher odds of cervical cancer (adjusted OR [aOR] = 1.043 per year; 95% CI: 1.004–1.083; $P = 0.030$ ).
Reproductive Factors: Earlier age at first pregnancy was independently associated with increased odds of cervical cancer (aOR = 0.918 per one-year increase in age at first pregnancy; 95% CI: 0.850–0.992; $P = 0.030$ ). This indicates that a younger age at first pregnancy correlates with higher risk.
Non-Associated Factors: No independent associations were found for body mass index (BMI), parity, age at menarche, smoking, hypertension, diabetes, abortion history, or oral contraceptive use after multivariable adjustment.
Model Performance: The final multivariable model demonstrated modest discriminatory ability (AUC = 0.666; 95% CI: 0.586–0.746) and satisfactory calibration (Hosmer–Lemeshow $P = 0.847$ ). The Nagelkerke $R^2$ was 0.100, indicating that the included variables accounted for approximately 10% of the variation in cervical cancer status. Internal validation via bootstrap resampling confirmed stable model performance (mean bootstrap AUC = 0.640).

Significance and Claims
The authors claim that this study provides rare population-based evidence from northeastern Iran, minimizing selection bias by sourcing both cases and controls from the same underlying population. The findings identify increasing age and earlier age at first pregnancy as independent risk factors, contributing to the understanding of cervical cancer etiology in this specific demographic.

The paper modestly concludes that while the predictive performance of the derived model is limited (likely due to the exclusion of critical variables such as HPV infection status, screening history, and socioeconomic data), the results offer a foundation for risk assessment and targeted prevention strategies in the region. The authors emphasize that these findings support the need for future prospective studies that incorporate HPV status, screening history, and broader socioeconomic determinants to improve risk prediction models and inform evidence-based public health planning. The study does not claim to establish causality due to its retrospective design but highlights the necessity of strengthening HPV vaccination, screening participation, and health literacy in line with WHO elimination strategies.

Technical Summary: Factors Associated with Cervical Cancer in Northeastern Iran

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